Neuroscience EXAM 2
Distinguish between declarative memory and nondeclarative (procedural) memory. Give examples of each.
Declarative memory is found to be in the cebral cortex.
4. Which mechanism would be a plausible explanation for synaptic depression? a. Inhibition of postsynaptic calcium channels b. Activation of presynaptic potassium channels c. Depletion of docked synaptic vesicles in the presynaptic terminal d. Faster replenishment of vesicles to the reserve pool e. Enhancement of presynaptic sodium currents Answer: c
Depletion of docked synaptic vesicles in the presynaptic terminal
What is step 1 of phase 1 of Long term Potentiation (LTP)
Depolarization of postsynaptic terminal
Which would be the most likely consequence of a mutation that renders DOPA decarboxylase inactive?
Dopamine would not be produced
which would be the most likely consequence of a mutation that renders DOPA decarboxylase inactive?
Dopamine would not be produced.
In which order are catecholamine neurotransmitters synthesized?
Dopamine, norepinephrine, epinephrine
in which order are catecholamine neurotransmitters synthesized?
Dopamine, norepinephrine, epinephrine
London taxi cab drivers must take a test of the city's 25,000 streets prior to becoming licensed. When the brains of these drivers are compared with control individuals, what difference is found?
Drivers have a larger posterior hippocampus than controls.
Which drosophila melanogaster genotype is associated with the worst preformance in an olfactory learning task?
Dunce, rutabaga double mutant
Signaling mechanisms underlying LTP.
During glutamate release, the NMDA receptor channel opens only if the postsynaptic cell is sufficiently depolarized. The Ca2+ ions that enter the cell through the channel activate postsynaptic protein kinases, such as CaMKII and PKC, that trigger a series of phosphorylation reactions. These reactions regulate trafficking of postsynaptic AMPA receptors through recycling endosomes, leading to insertion of new AMPA receptors into the postsynaptic spine. Subsequent diffusion of AMPA receptors to the subsynaptic region yields an increase in the spine's sensitivity to glutamate, which causes LTP.
What is the synaptic basis for short-term sensitization in Aplysia?
Modulatory interneurons strengthen synaptic transmission in the gill withdrawal circuit that is the synapses between the sensory and motor neurons of the siphon.
inositol triphosphate (IP3) receptor
IP3 binding mediates IP3R Ca2+ influx
Why is it thought that Ca levels might be involved in spike timing-dependent plasticity (STDP)?
If postsynaptic Ca2+ levels are high (as they are when presynaptic activity precedes postsynaptic potential) LTP occurs. If postsynaptic Ca2+ levels are low (as they are when postsynaptic potential precedes presynaptic activity) LTD occurs.
Being able to repeat a list of 10 words just after first being presented with them is an example of which type of memory?
Immediate memory
Distinguish between immediate, working (short-term), and long-term memory. Give an example of each.
Immediate memory is the routine ability to hold ongoing experiences in the mind for fractions of a second. An example would be recalling a sentence you just read in a book. Working memory is the ability to hold information in mind for seconds to minutes once the present moment has passed. Ex. looking for a lost object. Long-term memory entails the retention of information in a more permanent form of storage. Usually in an engram- the physical embodiment of the long-term memory in a neuronal machinery.
Forms of associative learning
Imprinting Conditioned Responses Instrumental conditioning Concepts
What is step 5 of phase 1 of Long term Potentiation (LTP)
Insertion of AMPA receptors
which molecule belongs to a class of cell associated signaling molecules?
Integrin
What is the main cause of myasthenia gravis symptoms
It an autoimmune neruomuscular disease that causes weakness in skeletal muscle
Why might a physician prescribe metoprolol rather than propranolol to treat high blood pressure?
It has fewer side effects because it selectively antagonizes β1-receptors.
Which statement about a nicotinic acetylcholine receptor at the neuromuscular junction is accurate?
It has two binding sites, and binding of two molecules of acetylcholine, one to each site, is required to activate the receptor.
Define synaptic potentiation
It is a form of short term synaptic plasticity that is elicited by repeated synaptic activity and serve to increase the amount of neurotransmitter released. Happens on a scale of ten seconds
Why can norepinephrine be considered a hormone?
It is released from the adrenal glands into the general circulation.
Why is the dendrite spine important
It receives the signal from the synapse
In which form of plasticity is this neural circuit involved, and which component of the circuit makes this form of plasticity possible?
It would decrease the rate of depression
Which characteristic of a living hippocampus slice is critically important to its suitability as a experimental system for studying learning?
Its architecture: the hippocampus can be sectioned without destroying relevant circuits.
Who invented Classical conditioning
Ivan Pavlov
long term synaptic depression in cerebellum
LTD requires depolarization of the purkinje cell, produced by climbing fiber activation, as well as signals generated by active parallel fiber synapses
Describe specificity in Long Term Potentiation
LTP induced by activation of one synapse does not occur in another (inactive) synapse. This property may be linked to a selective storage of information at synapses
Compare cellular mechanisms involved in LTP versus LTD?
LTP is accompanied by an increase in the number of postsynaptic AMPA receptors whereas LTD is accompanied by a decrease in the number of postsynaptic AMPA receptors.
. Compare cellular mechanisms involved in LTP versus LTD.
LTP is accompanied by an increase in the number of postsynaptic AMPA receptors, whereas LTD is accompanied by a decrease in the number of postsynaptic AMPA receptors.
input specificity
LTP is restricted to activated synapses rather than to all of the synapses on a given cell -if one pathway is weakly activated at the same time that a neighboring pathway onto the same cell is strongly activated, both synaptic pathways undergo LTP.
hebbian synapse
LTP occurs as a result of paired pre and postsynaptic stimulation
What would happen if Mg was not expelled from NMDA channels?
LTP would not occur
What characteristic makes Aplysia californica a practical model organism for studying the nervous system?
Large neurons
Conceptual learning
Learning in which animal (or human) is trained to classify objects. This type of learning emphasizes the kinds of things one is able to do with the information one has acquired. In monkeys and (probably humans as well), concept formation depends on activity in the prefrontal cortex of the brain.
Muscles in which region would most likely have the lowest density of muscle spindles?
Leg
What might LTP and epilepsy have in common?
Long-lasting or even permanent changes in neuronal circuitry underlie both LTP and epilepsy. Both also have an influx of calcium into the cell and there also may be larger dendritic spikes
What is the long-term depression (LTD)? How id is produced experiementally?
Long-term depression is a persistent activity-dependent weakening of synaptic transmission. It can be produced in the lab by stimulating Schaffer collaterals at a low frequency rate for a long period of time 10-15 minutes.
. What is long-term depression (LTD)? How is it produced experimentally?
Long-term depression is a persistent, activity-dependent weakening of synaptic transmission. It can be produced in the lab by stimulating Schaffer collaterals at a low frequency/rate for a long period of time /10-15 minutes.
Define long-term potentiation (LTP). Draw a diagram that shows how LTP is obtained experimentally in CA1 of the hippocampus.
Long-term potentiation represents a long-lasting increase in synaptic strength.
What changes occur in the brain as humans age?
Loss of synaptic connections decrease with age.
What triggers LTD?
Low-frequency stimulation followed by small or slow increase of Calcium
What are the main structural and functional differences between ionotropic and metabotropic receptors?
M: Are couples with G protein receptors- intracellular cascade, in channels (not specifically associated with ions) and slower I: Ligand gated that promote the flow of ions. faster
Which molecule binds NMDA receptors and prevents the flow of ions at resting at hyperpolarized membrane potentials?
Magnesium
GABA is inhibitory in
Mature neurons
Where is the hippocampus located?
Medial temporal lobe
Which afferents have the highest spatial resolution?
Merkel afferents
Who came up with instrumental conditioning?
Edward Thorndike
Which drug binds to the transmembrane domain of a GABAa receptor?
Ethanol
Define excitotoxicity. Why is it clinically important?
Excess extracellular concentration leads to uncontrolled continuous depolarization of neurons. Rises of intracellular calcium, with depolarization of nNOA, dysfunction of mitochondria, ROS production, ER stress and release of lysosomal enzymes.
Which pathway represents a route that pain info could take in the NS?
Free nerve ending receptor, unmyelinated C fiber axon, SC
Gq/11-PCR=
G-protein coupled5HT receptors
what is the main inhibitory neurotransmitter in the adult brain?
GABA
What are the two major inhibitory neurotransmitters in the adult CNS?
GABA and Glyine
Which receptor does the glycine receptor resemble structurally?
GABA-A
GTPase-activating proteins
GAPs -inactivate signal via GTP hydrolysis ex: Ras
Guanine nucleotide exchange factors
GEFs cause GTP exchange for GDP
G-coupled receptors (metobotrophic)
GTP-binding protein (or G-protein) is the transfusing molecule Ex: beta adrenergic receptor (binds epinephrines) muscarinic acetylcholine receptor, metabotrophic glutamate receptors, odorant receptors and more!
Where would the cell body of a sensory neuron that transmits touch information from the cheek to the CNS be located?
Ganglion alongside the brainstem
What is the main exicitatory neurotranmitter in the adult brain?
Glutamate
what is the main excitatory neurotransmitter in the adult brain?
Glutamate
Define and briefly describe the glutamate-glutamine cycle
Glutamate is taken up in the presynaptic neuron by NA-dependent glutamine uptake systems, where its converted to glutaminase. Extra and intra [glu] is modulated by XC-antiport. Neurotransmission ends by reuptake and NA dependent high-affinity glutamate membrane EAATs.
Mechanism underlying cerebellar LTD.
Glutamate released by parallel fibers activates both AMPA receptors and metabotropic glutamate receptors (mGluRs). The activated mGluRs produce two second messengers, DAG and IP3, which interact with Ca2+ that enters when climbing fiber activity opens voltage-gated Ca2+ channels. The resultant release of Ca2+ from the endoplasmic reticulum leads to a further rise in intracellular Ca2+ concentration and the activation of PKC, which triggers clathrin-dependent internalization of postsynaptic AMPA receptors, weakening the parallel fiber synapse.
Signaling at cerebellar parallel fiber synapses during long- term synaptic depression.
Glutamate released by parallel fibers activates both AMPA-type and metabotropic receptors. The latter produce IP3 and DAG in the Purkinje cell. When paired with a rise in Ca2+ associated with activity of climbing fiber synapses, the IP3 causes Ca2+ to be released from the endoplasmic reticulum, while Ca2+ and DAG together activate protein kinase C. These signals together change the properties of AMPA receptors to produce long-term depression.
For each of the neurotransmitters, lsit the precursers, rate-limiting enzyme of synthesis and mechanism of removal from teh synaptic cleft. GABA Glutamate Serotonin (5-HT) Acetylcholine (ACh) Dopamine (DA) Norepinephrine (NE)
Glutamate, GAD, Transporters Glutamine, Glutaminase, Transporters Tryptophan, Tryptophan hydrogenase, NAO or transporters Choline and Acyl CoA, CAT, ACheas Tyrosine, Tyrosine hydrogenase, Transports or monoamine oxidase Tyrosine, Tyrosine hydrogenase, Transports or monoamine oxidase
Which of the following is NOT a catecholamine?
Glutamine
molecular mechanisms of eCB-STD
Gq/11-PCR + increase in Ca2+ yields 2-AG is produced through a PLC beta dependent pathway because the receptor driven PLC beta stimulation is CA2+ dependent -the @-AG activates presynaptic CB1R, and induces transient suppression of transmitter release
What has patient H.M. taught us about human memory?
H.M taught neuroscientists the importance of the hippocampus in the brain
Which evidence best supports the idea that long-term declarative memories are not stored in the hippocampus?
H.M. could recall memories from his childhood.
Which statement about the clinical case of H.M. is false?
H.M.'s intellectual functions, as measured by intelligence tests, sharply declined after his surgery.
In Aplysia, short term synaptic depression due to reduced transmitter released exhibits?
Habituation
forms of non-associative learning?
Habituation Sensitization
A subject is asked to memorize a list of 15 words while being scanned in an fMRI machine. Where would you expect to see increased brain activity?
Hippocampus
Which genetic characteristic increases the risk of Alzheimer's disease, but is not sufficient to cause the disorder?
Homozygosity for the e4ApoE allele
What blocks the NMDA receptor
Mg2+
Which molecule binds NMDA receptors and prevents low of ions at resting and hyperpolarized membrane potentials?
Mg2+
which molecule binds NMDA receptors and prevents the flow of ions at resting and hyper polarized membrane potentials?
Mg2+
which molecule binds NMDA receptors and prevents the flow of ions at resting and hyperpolarized membrane potentials?
Mg2+
Give an example of habituation
Not feeling your cloth after some time period
What are the neural and behavioral symptoms of Alzheimer's disease? Briefly summarize the current view on the causes of Alzheimer's disease.
One of the first signs of Alzheimer's is the impairment of recent memory function and attention, followed by failure of language skills, visual-spatial orientation, abstract thinking, and judgment. Neural diagnosis looks at collections of intraneuronal cytoskeletal filaments, extracellular deposits of amyloid beta, and diffuse loss of neurons.
In classical conditioning, the subject learns that
One stimulus predicts another stimulus
Silent synapse (immature synapses) have _____ receptors.
Only NMDA Receptors
When do NMDA receptors open
Only during depolarization
A young child discovers that if he finds a specific black object and pushes a specific button, the television will come on. What type of learning is this?
Operant conditioning
activation of protein Kinases
PKA + cAMP = active CaMKII + Ca2+/CaM = active PKC + Ca2+ DAG = active MAPK + upstream kinases and ATP = active
Complete the sequence of events that take place in the presynaptic enhancement underlying short-term behavioral sensitization. Serotonin is released from facility interneuron; Calcium influx into the presynaptic terminal is enhanced; more neurotransmitter is released; synaptic transmission is enhanced
PKA signaling keeps presynaptic K channels closed.
complete sequence of events that take place in the presynaptic enhancement underlying short term behavioral sensitization: serotonin is released from facility interneuron; Ca2+ influx into the presynaptic terminal is enhanced; more neurotransmitter is released; synaptic transmission is enhanced;
PKA signaling keeps presynaptic K+ channels closed
during short-term behavioral sensitization: 1. serotonin is released from facility interneuron 2. Ca2+ influx into presynaptic terminal is enhanced 3. more neurotransmitter is released 4. synaptic transmission is enhanced what happens next?
PKA signaling keeps presynaptic K+ channels closed
What happens during Phase 2 of Long term Potentiation (LTP)
PKA, CREB-mediated changes in gene expression, Synthesis of New Proteins
Kinases that phosphorylate CREB
PKA, Ca2+/calmodulin kinase IV, and MAPK, phosphorylation allows CREB to bind to co-activators, which then stimulate RNA polymerase to begin synthesis of RNA
Afferent fibers that lack specialized receptors at their terminals detect which type of stimuli?
Pain
Which deficit would a lesion restricted to the right side of the spinal cord produce?
Pain deficit on the left side and mechanosensory deficit on the right side of the body
What is happening in Trial 14 of the experiment with elementary forms of behavior plasticity in Aplysia
Pairing shock tail with gill contaction results insame magnitude of gill contraction as in trial 1 due to sensitization(last for hours).
In specificity tell me the relationship between pathway 1 and pathway 2
Pathway 1: Active ( synapse strengthened) Pathway 2: Inactive ( synapse not strengthened)
In associativity tell me the relationship between pathway 1 and pathway 2
Pathway 1: strong stimulation ( synapse strengthened) Pathway 2: weak stimulation ( synapse strengthened) due to association If pathway 2 is weekly stimulated, it is not enough to create LTP. When you pair activity of Pathway 1 and Pathway 2 arriving to postsyanptic cell, you get LTP
List the steps underlying Long term Potentiation (LTP)
Phase 1 (2 hours) 1. Depolarization of postsynaptic terminal 2 NMDA receptor channels open and allow Ca2+ influx 3. Ca 2+ activates CaMKII 4. CaMKII phoshporylation of proteins, including AMPA receptors 5. Insertion of AMPA receptors Phase 2 PKA, CREB-mediated changes in gene expression, Synthesis of New Proteins
step 5 of presynaptic enhancement
More vesicles are fused
Rapidly adapting fibers are most likely to provide information about the _______ of a stimulus
Movement
Transcriptional regulation by CREB.
Multiple signaling pathways converge by activating kinases that phosphorylate CREB. These include PKA, Ca2+/calmodulin kinase IV, and MAPK. Phosphorylation of CREB allows it to bind co-activators (not shown in the figure), which then stimulate RNA polymerase to begin synthesis of RNA. RNA is then processed and exported to the cytoplasm, where it serves as mRNA for translation into protein.
Why does the function of GABAa receptors vary among neuronal types?
Multiple types of GABAa receptor subunits exist.
Which fibers conduct the sensation of first pain?
Myelinated A-delta
NMDA
N-methyl-D-aspartate possible subunits: (GluN1, GluN2A, GluN2B, GluN2C, GluN2D, GluN3A, GluN3B) -permeable to Ca2+, Na+, K+, and thus can affect Ca2+ dependent signaling -voltage gated (Mg2+ at hyper polarized Vm depolarization removes Mg2+ block from core) -require glutamate and depolarization for NMDAR allows for synaptic plasticity
In monkeys and probably humans as well, concept formation depends on activity in the ____ ____ of the brain.
Prefrontal Cortex
Short term synaptic plasticity is based on changes at
Presynapses
Long term synaptic plasticity is based on changes at
Presynapses and Postsynapse
step 4 of presynaptic enhancement
Presynaptic Ca 2+ increase
List the pathway that sensory input goes through
Primary Sensory Cortex --> Higher Order Sensory Cortex -> Polymodal and Association cortices --> Entorhinal cortex --> Perforant Path --> Hippocampal region <--> Subcortical inputs
Organization in which region of the brain is represented as a complete somatotopic map?
Primary somatosensory cortex S1
step 3 of presynaptic enhancement
Proteins (K+ channels) phosphorylation
mutations in _________ are found in Parkinson's patients
Rab5
Which of the following is not an example of declarative memory?
Remembering how to ride a bike
The alpha subunit of the G-protein is activated by ___________.
Replacing the GDP with GTP
SNAREs
SNAP receptors Vesicular SNARE forms a helical complex with Plasma Membrane SNAREs
Which substance is a neurotransmitter that stimulates merabotrpic 5-HT receptors, which have been implicated in circadian rhythm, satiety, motor behavior and emotinal state regulation?
Serotonin
Step 1 of presynaptic enhancement
Serotonin GPCR activation
short term sensitization mechanism
Serotonin released by the modulatory interneurons binds to G-protein-coupled receptors on the presynaptic terminals of the siphon sensory neurons (step 1), which stimulates production of the second messenger, cAMP (step 2). Cyclic AMP binds to the regulatory subunits of protein kinase A (PKA; step 3), liberating catalytic subunits of PKA that are then able to phosphorylate several proteins, probably including K+ channels (step 4). The net effect of the action of PKA is to reduce the probability that the K+ channels open during a presynaptic action potential. This effect prolongs the presynaptic action potential, thereby opening more presynaptic Ca2+ channels (step 5). There is ev- idence that the opening of presynaptic Ca2+ channels is also directly enhanced by serotonin. Finally, the enhanced influx of Ca2+ into the presynaptic terminals increases the amount of transmitter released onto motor neurons during a sensory neuron action potential (step 6).
Which sensation would an individual with anesthetized C fibers report when expose to intense heat?
Sharp pain only
In Aplysia, Enhancement ( Increased) glutamate release shows?
Short and long term sensitization
How are silent synapses converted to active excitatory synapses?
Silent synapses are turned "on" when (induced by LTP) AMPA receptors are added to postsynaptic membranes and the postsynaptic cell becomes responsive to glutamate.
8. How are silent synapses converted to active excitatory synapses?
Silent synapses are turned "on" when (induced by LTP) AMPA receptors are added to postsynaptic membranes, and the postsynaptic cell becomes responsive to glutamate.
The _______ is inversely proportional to the density of the fibers supplying an area
Size of the receptive field
monomeric G-proteins
Small G-protein -relay signals to intracellular targets -activated by GDP binding, GTP exchange -GEF cause GTP exchange for GDP -GAPs inactivate signal vis GTP hydrolysis
To which category of neurotransmitters does acetylcholine belong?
Small molecule neurotransmitters
Compare peptide transmitters with small-molecule neurotransmitters in terms of synthesis and removal from the synaptic cleft.
Small molecule neurotransmitters are synthesized in the cytoplasm of presynaptic terminal, while peptides are synthesized in ER.
Mechanism of action of NGF.
NGF binds to a high-affinity tyrosine kinase receptor, TrkA, on the plasma membrane to induce phosphorylation of TrkA at two different tyrosine residues. These phosphorylated tyrosines serve to tether various adapter proteins or phospholipase C (PLC), which in turn activate three major signaling pathways: the PI 3 kinase pathway leading to activation of Akt kinase, the ras pathway leading to MAPK, and the PLC pathway leading to release of intracellular Ca2+ from the endoplasmic reticulum and activation of PKC. The ras and PLC pathways primarily stimulate processes responsible for neuronal differentiation, whereas the PI 3 kinase path- way is primarily involved in cell survival.
During postsynaptic depolarization, what affects the membrane potential?
NMDA receptor and AMPA receptor as glutamate is released and reaches AMPA receptors at point where the postsynaptic membrane is depolarized. At this point, Ca 2+ is going in and Ca2+ is very inportant to support LTP. Ca2+ entering through NMDA is important for postsyanpse LTP.
What is step 2 of phase 1 of Long term Potentiation (LTP)
NMDA receptor channels open and allow Ca2+ influx
What are the three major types of ionotropic glutamate receptors, and why were they given their specific names? Why are two types of these receptors considered to be partiularly important?
NMDA- most central excitatory synapses AMPA- most central excitatory synapses Kainate *all ligand gates
Is single strong pre synaptic stimulus enough to cause LTP
NO
NMDA receptors are permeable to what ions
Na +, K+, Ca2+
GATs:
Na+ dependent co-transporters for GABA in neurons and glia
What causes synaptic depression
Tetanic stimulation causes all vesicles to released very fast. When presynaptic trerminal is stimulated with very high frequency, it causes immediate release of all vessicles that are ready to be released. It will cause synaptic facilitation; however, there is a depression (reduction) in the postsynaptic response. As a result of high frequency stimulation at the presynapse, there is a drastic reduction in postsynaptic responses. This is due to deplection of vesicies due to sustained presynaptic activity.
The axons of the medial lemniscus synapse with neurons of the _______
Thalamus
Glutamate synthesis and cycling between neurons and glia.
The action of glutamate released into the synaptic cleft is terminated by uptake into surrounding glial cells (and neurons) via excitatory amino acid transporters (EAATs). Within glial cells, glutamate is converted to glutamine by glutamine synthetase and released by glial cells through the SN1 transporter. Glutamine is taken up into nerve terminals via SAT2 transporters and converted back to glutamate by glutaminase. Glutamate is then loaded into synaptic vesicles via vesicular glutamate transporters (VGLUTs) to complete the cycle.
Amplification in signal transduction pathways.
The activation of a single receptor by a signaling molecule, such as the neurotransmitter norepinephrine, can lead to the activation of numerous G-proteins inside cells. These activated proteins can bind to other signaling molecules, such as the enzyme adenylyl cyclase. Each activated enzyme molecule generates a large number of cAMP molecules. cAMP binds to and activates another family of enzymes—the protein kinases—that can phosphorylate many target proteins. Although not every step in this signaling pathway involves amplification, overall the cascade results in a tremendous increase in the potency of the initial signal.
The biosynthetic pathway for the catecholamine neurotransmitters.
The amino acid tyrosine is the precursor for all three catecholamines. The first step in this reaction pathway, catalyzed by tyrosine hydroxylase, is rate-limiting.
A mouse is subjected to training while in a chamber with an electric grid on the floor that can deliver shocks to the mouse's feet. Whenever a blue light appears in the chamber, the mouse is given a shock, which elicits a freezing response in the mouse. How would you expect the mouse to behave after the training session?
The animal will freeze in response to the blue light alone.
What is synaptic plasticity?
The change that occurs at the synapses. Allows neurons to communicate with one another.
Cyclic AMP
Source: adenyl cyclase act on ATP, converts ATP to cAMP Intracellular targets: protein kinase A cyclic nucleotide-gated channels Removal mechanism: cAMP phosphodiesterase
Cyclic GMP
Source: guanylyl cyclase acts on GT, converts GTP to cGMP Intracellular targets: protein kinases G cyclic nucleotide-gated channels Removal mechanism: cGMP phosphodiesterase
IP3
Source: phospholipase C acts on PIP2 Intracellular targets: IP3 receptors on endoplasmic reticulum Removal mechanism: phosphates
Diacylglycerol
Source: phospholipase C acts on PIP2 Intracellular targets: protein kinase C Removal mechanism: various enzymes
Ca2+
Source: plasma membrane, IP3 receptors, ryanodine receptors Intracellular targets: calmodulin, protein kinases, protein phosphophatase, ion channels, synaptotagmins Removal mechanism: plasma membrane: Na+/Ca2+ exchanger, Ca2+ pump, endoplasmic reticulum: Ca2+ pump, Mitochondria ex: calmodulin, calbindin
Which sensation would be affected if group II sensory afferents in a limb were rendered dysfunctional due to a mutation?
Static posture of the limb
Over the course of 15 years, two individuals were asked to recall facts about a single life event. The data are presented above. What would explain the difference in results between the two subjects?
Subject A is a typical individual; subject B has superior autobiographical memory.
What is the basis of the windup form of central sensitization?
Summation of slow postsynaptic potentials in the dorsal horn of neurons
On which body part would the two-point discrimination threshold be shortest?
Thumb
What is the link between LTP and memory storage?
Time course and Mechanism
List the steps that occur during imprinting
Training onset -----> *C-fos gene expression up regulation in GABAergic Neurons *increase in the pool of releasable GABA *Phosphorylation of AMPA receptors *Postsynaptic density modifications *Phosphorylation of NMDA receptors -----> Stable recognition memory
What is instrumental conditioning called
Trial and error learning because the animal is free to try various responses before finding the one that is rewarded.
Where are the bodies of first-order neurons that conduct pain & thermal information from the face located?
Trigeminal ganglia & ganglia of CN VIII, IX, and X
What is the precursor of all catecholamines?
Tyrosine
Regulation of tyrosine hydroxylase by protein phosphorylation.
Tyrosine hydroxylase governs the synthesis of the catecholamine neurotransmitters and is stimulated by several intracellular signals. In the example shown here, neuronal electrical activity (1) causes influx of Ca2+ (2). The resultant rise in intracellular Ca2+ concentration (3) activates protein kinases (4), which phosphorylates tyrosine hydroxylase (5), stimulating catecholamine synthesis (6). This increased synthesis in turn increases the release of catecholamines (7) and enhances the postsynaptic response produced by the synapse (8).
At which point during the glutamate-glutamine cycle is postsynaptic gluamate action terminated rapidly?
Uptake of glutamate by the presynaptic terminal and glial cells
Give an example of sensitization
Walk in dark ally and hear noise. At light, you wouldn't notice it but at night, you sensitize and notice it because it becomes noxious
Mechanisms responsible for long lasting changes in synaptic transmission during LTP
The late component of LTP is the result of PKA activating the transcriptional regulator CREB, which turns on expression of several genes that produce long-lasting changes in PKA activity and synapse structure.
Which evidence suggests that short-term and long-term memory involve different brain mechanisms?
There are neuroimaging studies show that declarative memories are stored in specialized areas of the cerebral cortex. Retrieving memories are stored in the medial temporal lobe and front cortex. Frontal cortical areas located on the dorsolateral anterlateral aspect of the brain.
Why does shocking the tail will gill contraction increase the magnitude of gill contraction
There is an interneuron which sensory neuron make contact with. Sensory neuron activation will lead to contraction of muscle due to activation of motor neuron. Tail muscle innervated with other sensory neurons that make contract with another modulatory interneuron which is serenorigic and this modulatory neuron preynaptically regulates the synaptic release of first neuron onto motor neuron and gill.
Which statement about muscarinic acetylcholine receptors is true?
They are metabotropic receptors
How do he short-term forms of synaptic plasticity contribute to learning and memory?
They cause the transmission at chemical synapses to change dramatically as a consequence of the recent history of synaptic activity that is experienced.
. How do the short-term forms of synaptic plasticity contribute to learning and memory?
They cause the transmission at chemical synapses to change dynamically as a consequence of the recent history of synaptic activity, that is, experience.
Monoamien oxidase inhibitors are sometimes used in the treatment of parkinson's disease/ What is their mechanism of action?
They inhibit they breakdown of dopamine
Which kinase is activated by the phosphorylation of its activation loop? a) CaMKII b) protein tyrosine kinase c) PKA d) PKC e) MAPK
a
Which of the following is the first step in the nuclear signaling process? a) binding of transcriptional activator protein b) transcription c) chromatin decondensation d) binding of RNA polymerase e) binding of co-activator complex
a
Which protein kinase is the primary effector of cAMP? a) PKA b) CaMKII c) MAPK d) protein tyrosine kinase e) PKC
a
Which role does calmodulin play in the intracellular cascade triggered by Calcium? a) it binds to its downstream targets when activated by calcium b) it enhances downstream effects of calcium c) it serves as a calcium buffer d) it modulates the strength of calcium binding to its downstream targets e) it serves as a calcium sensor when neurotransmitter is released
a
benzamidine
a GABAa receptor agonist
Parallel fiber
a fiber originating in the granule cells of the cerebellum that synapses on the Purkinje cells
Mechanisms underlying LTD
a low amplitude rise of Ca2+ concentration in the post synaptic CA1 neuron activates postsynaptic protein phosphatases, which cause internalization of postsynaptic AMPA receptors, thereby decreasing the sensitivity to glutamate released from the Schaffer collateral terminals
Which statement about the plasticity of synapses in the mammalian CNS is false? a. The hallmark of both short-term and long-term synaptic plasticity is that they always increase the strength of synaptic connections. b. The efficacy of synapses can be adjusted by modulating the amount of neurotransmitter that is released. c. Calcium ions play a central role in at least some forms of synaptic plasticity. d. Changes in synaptic efficacy can occur over time scales ranging from milliseconds to years. e. A variety of molecular mechanisms are involved in the different forms of synaptic plasticity. Answer: a
a. The hallmark of both short-term and long-term synaptic plasticity is that they always increase the strength of synaptic connections.
. After firing a short burst of action potentials in an axon, researchers observe a larger EPSP in the postsynaptic cell, and this effect seems to last a few tens of milliseconds. This is most likely due to the presynaptic terminal having a. extra calcium. b. lowered calcium. c. extra sodium. d. reduced sodium. e. extra magnesium. Answer: a
a. extra calcium.
. LTP represents a lasting increase in the size of EPSP a. following a high-frequency train of stimuli. b. following a low-frequency train of stimuli. c. following a single stimulus. d. that is restricted to the hippocampus. e. that is restricted to the cortex. Answer: a
a. following a high-frequency train of stimuli.
. Cerebellar LTD depends on a. synergistic actions of calcium and IP3 on internal calcium release channels. b. synergistic actions of sodium and IP3 on internal calcium release channels. c. activation of AMPA receptors by voltage-gated ion channels. d. binding of IP3 to clathrin to activate endocytosis. e. calcium-dependent insertion of GABA receptors into the postsynaptic membrane. Answer: a
a. synergistic actions of calcium and IP3 on internal calcium release channels.
Give an example of a nuerotranmistter in each category below: a.) Purine b.) Biogenic amine c.) Amino Acid d.) Peptide
a.) ATP b.) epinephrine, dopamine c.) Glutamate, GABA d.) neuropeptide gamma
Normal levels of Ca2+ will result into
a strong and fast depression
synaptic plasticity
a type of information storage
. What is needed for: a) the initial acquisition of LTP and b) the maintenance of long-lasting LTP?
a) Increase in postsynaptic Ca2+ b) Increase in the number of postsynaptic AMPA receptors with subsequent changes in protein expression in the postsynaptic cell
What is needed for: a.) the initial acquisition of LTP and b.) the maintenance of long-lasting LTP?
a) Increase in postsynaptic Ca2+ b) Increase in the number of postsynaptic AMPA receptors with subsequent changes in protein expression in the postsynaptic cell
4. How would an increase in external Ca2+ concentration affect synaptic depression? a. It would increase the rate of depression. b. It would reduce the rate of depression. c. It would decrease the rate of neurotransmitter release and induce depression. d. It would increase the rate of neurotransmitter release and delay depression. e. It would have no effect on depression.
a. It would increase the rate of depression.
Which characteristic of a living hippocampus slice is critically important to its suitability as an experimental system for studying learning? a. Its architecture: the hippocampus can be sectioned without destroying relevant circuits. b. The hippocampus contains few neurons, which makes it easy to study. c. The layer of the pyramidal neurons is divided into several regions. d. Long-term potentiation takes place in hippocampal synapses. e. The hippocampus is involved in learning. Answer: a
a. Its architecture: the hippocampus can be sectioned without destroying relevant circuits.
Phospholipase C (PLC)
activated by G-proteins and calcium to cleave PIP2 (membrane lipid) into IP3 and inositol, both of which act as a second messenger
Diacylyglycerol (DAG):
activated by PLC, can activate PKC
intracellularreceptors
activated by cell-permeant lipophilic signaling molecules -many lead to gene expression -many are bound to inhibitory complex, which dissociates upon ligand binding to expose DNA-binding domain, acting as transcription factor ex: steroid hormone receptors
Ryanodine receptor
activated indirectly by cytoplasmic Ca2+, implicated in caffeine signaling
climbing fiber glutamate release
activates: *AMPARs -> depolarization *VGCC -> increase [Ca2+] *IP3 + Ca2+ -> massive increase in [Ca2+] which eventually leads to AMPAR internalization
parallel fibers glutamate release
activates: *AMPARs -> depolarization *mGluRs -> IP3 -> increase in [Ca2+] *mGluRs -> DAG -> PKC that eventually lead to AMPAR internalization
slow transmission example
adrenal medullary hormones (epinephrine and norepinephrine) secreted during stressful events are slower and have longer lasting effects on muscle metabolism and emotional state
asynchronous fusion of synaptic vesicles occurs
after the initial stimulation-induced synchronous fusion
synaptic vesicle retrieval (e.g. synaptic vesicle recycling via endocytosis) involves
all of the above clathrin, dynamin, the plasma membrane
the endocannabinoid system is involved in
all of the above learning, drug addiction, feeding behavior, analgesia
Ca2+ independent endocannibinoid release can be driven by
all of the above: mGluRs, 5HT2 type serotonin receptors, oxytocin receptors
the snare complex is composed of
all the above snaptobrevin on the synaptic vesicle, syntaxin-1 on the plasma membrane, snap-25 on the plasma membrane,
Ca2+/calmodulin-dependent protein kinase, type II (CaMKII)
allows synapsin to dissociate from the vesicles
Clathrin
along with other proteins form coated pits that initiate membrane budding
to which subunit(s) of heterotrimeric G-protein does guanine nucleotide bind?
alpha
to which subunits of heterotrimeric G-protein does a guanine nucleotide bind?
alpha
AMPA
alpha amino-3-hydroxyl-5-methyl-4-isoazole-propionate) -structure of AMPA receptor: combination of 4 possible subunits (GluA1, GluA2, GluA3, GluA4) in tetramer confer functional properties such as ion selectivity -binding of glutamate causes gate helices within transmembrane domain to move and thereby open channel pore (binding of glutamate closes the clamshell structure of the LBD, leading to movement of the gate helices that opens the channel pore. -largest part of each subunit is extracellular, consists of 2 domains the amino terminal domain (ATD) and the ligand bind domain (LBD) the transmembrane domain (TMD) forms part of the ion channel pore and an intracellular carboxyl-terminal domain (CTD) connects the receptor to the intracellular proteins
which toxin blocks neuromuscular transmission by irreversibly binding to nicotine acetylcholine receptors, thus preventing acetylcholine from opening postsynaptic ion channels?
alpha- bungarotoxin
Which toxin blocks neurotransmission by irreversibly binding to nicotinic AChRs, thus preventing ACh from opening postsynaptic ion channels?
alpha-bungarotoxin
Histamine:
also mediates allergic responses antagonists also are used to prevent motion sickness via modulating vestibular function synthesis of histamine: from histidine + histadine decarboxylase yields histamine
Glutamate
amino acid = small molecule transmitter post synaptic effect = excitatory precursor = glutamine rate limiting step = glutaminase removal mech = transporters type of vesicle = small, clear
GABA
amino acid = small molecule transmitter post synaptic effect = inhibitory precursor = glutamate rate limiting step = GAD removal mech = transporters type of vesicle = small, clear
Glycine
amino acid = small molecule transmitter post synaptic effect = inhibitory precursor = serine rate limiting step = phosphoserine removal mech = transporters type of vesicle = small, clear
What is the main cause of myasthenisa gravis?
an autoimmune reaction against nAChRs
Define sensitization
an increase in the response to an innocuous (non-noxious) stimulus when that stimulus coincides with a noxious (ex. punishing stimulus) It allows to generalize an aversive response elicited by a noxious stimulus to a variety of non noxious stimuli
anisomycin
an inhibitor of protein synthesis -causez LTP to decay within a few hours
Hypertension and _______ can be treated with β-receptor antagonists (beta blockers).
anxiety
Noradrenergic receptors:
are metabotropic.
NO synthesis, release and termination
arginine + NO synthase = NO (and citrulline... but we don't care about this yet)
LTD and LTP
associated with many molecular mechanisms
Classical (Pavlovian) conditioning involves
associating stimulus that evokes a response (=unconditional stimulus) with a second (conditional) stimulus that normally doesn't evoke this response.
The β2-receptor agonist albuterol is used to treat _______ because it _______.
asthma; relaxes the bronchial muscles and creates a wider airway
which of the following provides an example of a second messenger producing another second messenger? a) diacylglycerol fuses with PIP2, producing IP3 b) IP3 binds to its receptor, enabling the release of calcium from the cytosol c) G-proteins activate adenylyl cyclase in the plasma membrane causing it to produce cyclic nucleotides d) Calcium binds to calmodulin, promoting its binding to downstream protein kinases e) phospholipase C acts on PIP 2, splitting it into IP3 and diacylglycerol
b
which statement about protein kinase-based signaling is false? a) the effects of protein kinases can be balanced by protein phosphatases b) each protein kinase has just one specific target protein that it phosphorylates c) thousands of protein kinases are expressed in the brain d) serine and threonine kinases are typically activated by second messengers e) tyrosine kinases are typically activated by extracellular signals
b
. What characteristic(s) make(s) Aplysia californica a practical model organism for studying the nervous system? a. Its great magnitude and variety of neurons b. Its large neurons c. The random location of its neurons d. That it is aquatic e. All of the above Answer: b
b its large neurons
(e)
at certain types of synapses, synaptic stimulation induces a novel type of postsynaptic long term depression (LTD), which is CB1R independent, TRPV1 dependent and anandamide dependent
myasthenia gravis (MG)
autoimmune disease of neuromuscular synapses -caused by antibodies directed AChR -treated (partially restored with AChE blockers such as neostigmine
what is the main cause of myasthenia gravis symptoms?
autoimmune reaction against nicotinic acetylecholine receptors
sensitization
aversive response elicited by noxious stimulus generalized to non-noxious stimuli ex. aplysia withdraws gill when siphon tough is paired to tail shock
Complete the sequence of events that take place in the presynaptic enhancement underlying short-term behavioral sensitization: Serotonin is released from facilitatory interneuron; Ca2+ influx into the presynaptic terminal is enhanced; more neurotransmitter is released; synaptic transmission is enhanced a. IP3 signaling keeps postsynaptic K+ channels closed. b. IP3 signaling keeps presynaptic K+ channels closed. c. PKA signaling keeps presynaptic K+ channels closed. d. PKA signaling keeps presynaptic K+ channels open. e. cAMP signaling keeps presynaptic K+ channels open. Answer: c
c. PKA signaling keeps presynaptic K+ channels closed.
15. Silent synapses are "silent" because they a. have no presynaptic terminal. b. have AMPA receptors but no NMDA receptors. c. have NMDA receptors but no AMPA receptors. d. lack voltage-gated sodium channels. e. are continuously inhibited and so cannot be activated. Answer: c
c. have NMDA receptors but no AMPA receptors.
Step 2 of presynaptic enhancement
cAMP -activation of Pka
CREB
cAMP response element binding protein, transcriptional activator
CRE
cAMP response element, DNA binding site for CREB
which second messenger originates from both extracellular and intracellular compartments?
ca2+
PP1:
can influence neuronal electrical signaling by dephosphorylating K+ and Ca2+ channels
NO (nitric oxide)
can permeate the plasma membrane, has a range of influence that extends well beyond the cell of origin, diffusing a few tens of micrometers from. -makes NO a potentially useful agenda for coordinating multiple cells in a localized region
. The type of receptor that is critical for the induction of hippocampal LTP, admitting calcium into a dendritic spine, is called a(n) a. AMPA receptor. b. NMDA receptor. c. glycine receptor. d. cholinergic GPCR. e. noradrenergic GPCR. Answer: b Textbook Reference
b. NMDA receptor.
. Which mechanism contributes to the long-term enhancement of the gill withdrawal reflex in Aplysia but is not involved in the short-term enhancement of the reflex? a. Activation of G-protein-coupled receptors by serotonin b. Phosphorylation of CREB c. Activation of adenylyl cyclase d. Activation of protein kinase A e. Decreased opening of potassium channels during presynaptic action potentials Answer: b
b. Phosphorylation of CREB
Which statement describes the depicted phenomenon most accurately? a. Synaptic depression directly correlates with the concentration of extracellular Ca2+. b. Synaptic depression directly correlates with the amount of neurotransmitter released. c. Synaptic depression is inversely correlated with the amount of neurotransmitter released. d. Synaptic depression depends on the rate of neurotransmitter release. e. Synaptic depression depends on the concentration of neurotransmitter in synaptic vesicles.
b. Synaptic depression directly correlates with the amount of neurotransmitter released.
. Which statement about silent synapses is true? a. They cannot be induced to transmit information. b. They transmit information at a resting membrane potential. c. They can produce postsynaptic responses as a result of LTP. d. They contain both NMDA and AMPA receptors. e. They represent mature glutamatergic synapses. Answer: b
b. They transmit information at a resting membrane potential.
2. Firing an action potential in an axon initially causes a 10-mV depolarization (EPSP) in a postsynaptic neuron, but after applying a certain stimulus to the axon, firing it causes an 8-mV depolarization after each action potential. This phenomenon is called synaptic a. enhancement. b. depression. c. facilitation. d. augmentation. e. potentiation. Answer: b
b. depression.
. The key aspect of receptor-gating in the associative induction of hippocampal LTP is that a. all glutamate receptors open automatically whenever glutamate is in the synaptic cleft. b. the NMDA receptor acts as a molecular coincidence detector. c. the AMPA receptor allows calcium into the cell only after the NMDA receptor is activated. d. both the NMDA and AMPA channels must be open in order for the cell to depolarize. e. The NMDA receptor allows the flow of magnesium into the cell. Answer: b
b. the NMDA receptor acts as a molecular coincidence detector.
gating of the AChR
binding of Each to its binding sites on the 2 alpha subunits causes a conformational change in part of the extracellular domain-> the pore forming helices to move and open the pore gate
calmodulin:
binds Ca2+ activates other downstream targets such as synaptotagmins
Catecholamines
biogenic amines = small molecule transmitter post synaptic effect = excitatory precursor = tyrosine rate limiting step = tyrosine hydroxylase removal mech = transporters, MAO, COMT type of vesicle = small, dense core, or large irregular dense core
in what way are GABA and glutamate similar in the adult brain?
both are common in the nervous system.
How are glutamate and GABA similar?
both found in the nervous system
glutamic acid decarboxylase (GAD)
catalyze the conversion of glutamate to GABA -requires pyridoxal phosphate (vitamin B6 derivative) for activity
tyrosine hydroxylase:
catalyzes synthesis by producing dihydroxyphenylalanine (DOPA)
Acetyltransferase
catalyzes synthesis of acetylcholine from Choline and acetyl CoA
Hydroxymethyltransferase
catalyzes synthesis of glycine from serine
which process differentiates long term and short term sensitization?
changes in gene expression
which type of signaling do mature neurons most commonly use to communicate?
chemical only
Synaptic plasticity can lead to changes in ______ and ultimately to _________
circuit function behavior plasticity
botulinum toxin blocks vesicle release by
cleaving DSNARE proteins
interesting transcription factors in the brain
condensed chromatin is decondensed into a bears on a dan string array in which an upstream activator site is free of proteins and is bound by a sequence-specific transcriptional activator protein (a transcription factor). the transcriptional activator protein then binds co-activator complexes that enable the RNA polymerase with its associated factors to bind at the start site of transcription and initiate RNA synthesis
Serotonin ionotropic receptors
consists of 5 subunits each has an extracellular domain, transmembrane domain, and an intracellular domain. an ion channel is formed by the transmembrane domains of the 5 subunits
Synaptic connectivity between neurons is ________
constantly changing in response to neural activity
Which substancce is a second messenger whose activity is terminated by a phosphatase? a) diacylglycerol b) CAMP c) inositol trisphosphate d) cGMP e) calcium
c
To which subunit(s) of heterotrimeric G-protein does a guanine nucleotide bind? a) beta b) βγ subunit complex c)γ d) α e) δ
d
which of the following is the first step in the process of activation of a heterotrimeric G-protein? a) the α subunit dissociates from the βγ complex b) the α subunit binds to downstream effector molecules c) the α subunit binds to GDP d) the G-protein binds to the activated receptor e) the α subunit binds to β and γ subunits to form the inactive trimer.
d
phosphodiesterase
convert cAMP into AMP or cGMP into GMP to deactivate signal
glutamine synthetase:
converts glutamate to glutamine
. Which statement about long-term synaptic plasticity is false? a. The efficacy of transmission at many synapses depends on their history of synaptic activity. b. The tracking of long-term changes in synaptic efficacy is difficult in mammalian systems because of the complexity of mammalian brains. c. The gill withdrawal reflex in Aplysia can be enhanced by pairing a noxious stimulus with a mild touch. d. Associative learning in the Aplysia gill withdrawal reflex is relatively independent of the timing or the order in which different stimuli are applied. e. Gill withdrawal behavior in Aplysia can be altered for days or weeks by means of repeated pairings of shocks and touches. Answer: d
d. Associative learning in the Aplysia gill withdrawal reflex is relatively independent of the timing or the order in which different stimuli are applied.
. Which second messenger(s) is(are) involved in postsynaptic depression? a. Ca2+ only b. cAMP and Ca2+ only c. DAG and IP3 only d. Ca2+, DAG, and IP3 e. cAMP, Ca2+, DAG, and IP3 Answer: d
d. Ca2+, DAG, and IP3
Which mechanism used in hippocampal LTD is not part of the hippocampal LTP mechanism? a. History-dependent modification of synaptic efficacy b. NMDA receptor activation c. Calcium influx d. Calcium-dependent activation of protein phosphatases e. Calcium-dependent activation of protein kinases. Answer: d
d. Calcium-dependent activation of protein phosphatases
. What triggers LTD? a. Ca2+ influx into the postsynaptic terminal b. Internalization of AMPA receptors c. High-frequency stimulation d. Low-frequency stimulation followed by small or slow increase in Ca2+ e. Low-frequency stimulation followed by sharp and dramatic increase in Ca2+ Answer: d
d. Low-frequency stimulation followed by small or slow increase in Ca2+
Learning and memory processes in the fruit fly Drosophila show striking molecular overlap with analogous processes in Aplysia, in terms of their using all of the following except a. phosphodiesterase. b. adenylyl cyclase. c. adenylyl cyclase activating pathways. d. allosteric modulation of GABA receptors. e. CREB gene regulation. Answer: d
d. allosteric modulation of GABA receptors.
In which form of plasticity is this neural circuit involved, and which component of the circuit makes this form of plasticity possible? a. Habituation; interneuron b. Habituation; modulatory interneuron c. Sensitization; interneuron d. Sensitization; modulatory interneuron e. Sensitization; motor neuron
d, sensation modulatory interneuron
11. You are examining long-term potentiation in two groups of hippocampal neurons: control and treated. You induce lasting LTP in the control cells after repetitive high-frequency stimulation. In the treated cell, however, the potentiation begins to decrease after 2 hours. What treatment was given? a. A drug that blocks sodium channels b. A drug that opens calcium channels c. A drug that binds magnesium d. A drug that inhibits protein synthesis e. A drug that blocks clathrin Answer: d
d. A drug that inhibits protein synthesis
mechanism of long term sensitization
due to changes in gene expression, resulting in the synthesis of proteins that change PKA activity and lead to changes in synapse growth 1. serotonin GPCR activation 2. cAMP production 3. PKA activation 4. CREB phosphorylation 5. CRE dependent gene Transcription 6. ubiquitin hydrolase degrades regulatory subunit of PKA activity even in Absence of nerve impulse 7. Other unknown genes increase synapses between sensory and motor neuron 8. cytoplasmic polyadenylation element Binding protein (CPEB) activates mRNAs
Ca2+ triggered vesicle fusion
during docking of the synaptic vesicle, SNARE proteins on the vesicle and the plasma membranes form a complex that brings together the two membranes. Synaptotagmin binds to this SNARE complex. subsequent binding of Ca2+ to synaptotagmin causes the cytoplasmic region of this protein to insert into the plasma membrane to produce the membrane curvature that catalyzes membrane fusion. fusion of membranes leads to exocytotic release of neurotransmitter
signaling mechanisms underlying LTP
during glutamate release, the NMDA receptor channel opens only if the postsynaptic cell is sufficiently depolarized. the Ca2+ ions that enter the cell through the channel activate postsynaptic protein kinases, such as CaMKII and PKC, that triggers a series of phosphorylation reactions. these reactions regulate trafficking of postsynaptic AMPA receptors through recycling endoscopes, leading to insertion of new AMPA receptors into the postsynaptic spine. subsequent diffusion of AMPA receptors to the subsynaptic region yields an increase in the spines's sensitivity to glutamate, which causes LTP
presynaptic vesicle retrevial machinery
dynamin is well established as being responsible for scission of nascent vesicles from presynaptic membrane -dephosphorylation of proteins by calcineurin is an important regulatory step in synaptic vesicle endocytosis
Postsyanptic glutamate receptors are
dynamitically regulated at excitatory synapses
aplysia neurons
few tens of thousands -large (up to 1 mm in diameter) -stereotyped locations of neurons facilitates mapping of structure to function
AChR
five subunits : 2 alpha, beta, gamma, and 2 types: nicotinic AChR: agonize by nicotine muscarinic AChR: agonized by muscarine from the poisonous red mushroom amanita -both toxins are stimulants that produce nausea, vomiting, mental confusion, and convulsions -muscarine can also lead to circulatory collapse, coma, and death
LTP represents a lasting increase in the size of EPSP
following a high frequency train of stimuli
LTP represents a lasting increase in the size of EPSP
following a high-frequency train of stimuli
(LTD) long-term synaptic depression:
form of synaptic plasticity that weakens these synapses -LTD is induced climbing fiber synapses also activated *produce large EPSPs, Ca2+ enters V-gated Ca2+ channels *intracellular Ca2+ stores released *activation of second messenger signaling leads to long term changes
dynamin
forms ring like coil that surrounds the lipid stalk causing final pinching off of membrane
alpha- bunarotoxin:
found in snake venom, used by snare to paralyze its prey. blocks neuromuscular transmission by irreversibly binding to nACh Receptors
Syntaxin and SNAP-25:
found primarily on the plasma membrane
which statement about dendritic spines is false? a) they slow the diffusion of IP3, but do not prevent it from leaving the spine b) they have a bulbous head connected to a dendritic shaft by a narrow neck c) they are the sites of excitatory synapses in various parts of the CNS d) they enable localized, transient increases in calcium e) they usually contain just three proteins: NMDA receptors, mGluR receptors, and CaM kinase II
e
. Which type of short-term synaptic plasticity lasts the longest? a. Potentiation b. Augmentation c. Depression d. Facilitation e. Post-tetanic potentiation
e,
. Which condition(s) must be met to induce LTP? a. Glutamate must be released from the presynaptic terminal. b. Glutamate must open the postsynaptic AMPA receptors. c. The postsynaptic membrane must be depolarized for a period of time. d. Mg2+ block must be expelled from NMDA receptors to allow Ca2+ influx. e. All of the above Answer: e
e. All of the above
. What would happen if Mg2+ was not expelled from NMDA channels? a. Glutamate would not bind to NMDA receptors. b. Glutamate would not bind to AMPA receptors. c. The postsynaptic membrane would not depolarize. d. EPSP would not occur. e. LTP would not occur. Answer: e
e. LTP would not occur
The targets of the phosphatases activated during hippocampal LTD are a. voltage-gated ion channels. b. ligand-gated ion channels. c. synaptic vesicle regulatory proteins. d. postsynaptic signaling pathways. e. unknown. Answer: e
e. unknown.
(a)
eCB activates presynaptic CB1R and suppress LTP
(b, b')
eCBs activated CB1R of nearby interneurons and activate K+ channels, decrease in firing rate, influences activity of target neurons (b')
(d, d')
eCBs activated astrocytic CB1R which leads to increase in Ca2+ levels which leads to glutamate release, where it potentiates the excitatory transmission via presynaptic group 1 mGluRs
dunce:
encodes a phosphodiesterase (which degrades cAMP)
Rutabaga
encodes adenylyl cyclase
amnesiac
encodes peptide transmitter that stimulates adenylyl cyclase
endorphins
endogenous compounds that mimic morphine ex. alpha endorphin alpha neoendorphin beta endorphin gamma endorphin
anandamide and 2-arachidonoylglycerol (2-AG):
endogenous compounds which activate cannabinoid receptor
Which drug binds to the transmembrane domain of a GABA-A receptor?
ethanol
The GABA derivative gamma-hydroxybutyrate causes ______
euphoria and memory deficit
short term plasticity
facilitation depression augmentation potentiation
NMDA receptor channel can only open during depolarization of the postsynaptic neuron fro its normal resting potential
depolarization expels Mg2+ from the NMDA channel, allowing current to flow into the postsynaptic cell. this leads to Ca2+ entry, which triggers LTP -blocking NMDARs prevent LTP -NMDA receptor channel is permeable to Ca2+ but is blocked by Mg2+ at rest -the NMDA receptor channel can open only during depolarization of the postsynaptic neuron from its normal resting potential -properties of the NMDA receptor can account for many of the characteristics of LTP
What is the most likely consequence of a mutation that renders DOPA decarboxylase inactive?
dopamine would not be produced
In which order are the catecholamines synthesized?
dopamine, norepinephrine, epinephrine
postsynaptic density
dozens of proteins involved in intracellular signal transduction
mechanism of short term sensitization
due to acute, PKA- dependent enhancement of glutamate release from presynaptic terminals of sensory neurons 1. serotonin GPCR activation 2. cAMP production 3. PKA activation 4. K channel phosphorylation, prolonged APs 5. more presynaptic Ca2+ channel activation 6. more transmitter released onto motor neurons
in which direction do Ca2+ ions flow through ryanodine receptors?
from the endoplasmic reticulum into the cytoplasm
Long term plasticity requires changes in
gene expression, new protein synthesis, and growth (or elimination) of new synapses
What is the main excitatory neurotransmitter in the brain?
glutamate
Which neurotransmitter is released at the majority of brain synapses, making is the most abudant neurotransmitter in the nervous system?
glutamate
Which neurotransmitter is the most abundant in the nervous system, as it is released at the majority of brain synapses?
glutamate
what is the main excitatory neurotransmitter in the adult brain?
glutamate
mechanisms underlying cerebellar LTD
glutamate released by parallel fivers activate both AMPA and metabotrophic glutamate receptors (mGluRs). the activated mGluRs produce two second messengers, DAG and IP3, which interact with Ca2+ that enters when climbing fiber activity opens voltage gated Ca2+ channels. the resultant release of Ca2+ from the ER leads to further rise in intracellular Ca2+ concentration and the activation of PKC, with triggers clathrin dependent internalization of postsynaptic AMPAreceptors, weakening the parallel fiber synapse
Glycine
glycine can be synthesized by several metabolic pathways; in the brain, the major precursor is serine.
tyrosine hydroxylase:
governs the synthesis of catecholamine -activity increased by phosphorylation -phosphorylation associated with electrical activity, neurotransmitters, NGF, PKA, CaMKII, MAPK, and PKC. cAMP, Ca2+ or DAG
long term plasticity
habituation sensitization short term memory long term memory
depression
high frequency stimulation leads to exhaustion of synaptic vesicle supply and reduced EPSCs -progressive depletion of pool of synaptic vesicles that are available for release. -lowering external Ca2+ reduces number of quanta released after AP -for normal [Ca2+]: SV pool depletes, reduced EPSCs -for intermediate [Ca2+]: lower Ca2+, less SV depletion, but Ca2+ accumulates giving a mixed depression and augmentation
facilitation:
high frequency stimulation leads to presynaptic Ca2+ accumulation and increased EPSC. Ca2+ activates Synaptotagmin-7 on plasma membrane and triggers neurotransmitter release over timescales of tens of msec -prolonged elevation of presynaptic calcium levels following synaptic activity leads to larger EPSP -entry of Ca2+ into the presynaptic terminal occurs with 1 to 2 milliseconds, but return of Ca2+ to resting levels is much slower -calcium builds up, allows more neurotransmitter release by next AP
biogenic amines
histamine, serotonin
synthesis, release, and reuptake of glycine
hydroxymethyltranferases catalyzes the synthesis of glycine from serine -transported into synaptic vesicles via the same transporters as GABA (loaded into synaptic vesicles via vesicular inhibitory amino acid transporter) -pentamers with mixtures of 4 alpha subunits, along with an accessory beta subunit
histamines
imidazoleamines = biogenic amine= small molecule transmitter post synaptic effect = excitatory precursor = histidine rate limiting step = histidine decarboxylase removal mech = transporters type of vesicle = large, dense cores
PP2A
implicated in Alzheimer's disease via excessive phosphorylation tau
Long term synaptic Depression (LTD)
in hippocampus, selectively weakens specific sets of synapses -LTD occurs with low frequency stimulation (1Hz) for long periods (10-15 mins) -LTD and LTP can negate each other -Large and fast rises in Ca2+ lead to LTP -small and slow rises in Ca2+ lead to LTD -LTD results from *activation of phosphates PP1 and PP2B (calcineurin, Ca2+-dependent) *AMPAR endocytosis
Define synaptic augmentation
increase in synaptic strength where synaptic plasticity occurs on a scale of a few seconds
signal amplification
individual signaling reactions create more products than molecules requires to initiated reactions
serotonin
indoleamine = biogenic amine = small molecule transmitter post synaptic effect = excitatory precursor = tryptophan rate limiting step = tryptophan hydroxylase removal mech = transporters, MAO type of vesicle = large dense cores
amphetamines:
inhibit dopamine cotransporter (DAT), and thereby increases dopamine concentrations in the synaptic
What is the mechanism of organophosphate toxicity?
inhibition of acetylcholinesterase
what is the mechanism of organophosphate toxicity?
inhibition of acetylcholinesterase
The major difference between D1 and D2 dopamine receptor subtypes is that one _____.
inhibits and the other stimulates adenylyl cyclase and cAMP.
the figure shows an electron micrograph of a chemical synapse in the cerebral cortex. which statement about this synapse is accurate
inside the presynaptic neuron are synaptic vesicles, which fuse with the membrane in the active zone
Cell-permeant signaling molecules bind to which type of receptor?
intracellular
enzyme linked receptors
intracellular domain is an enzyme -catalytic activity regulated by extracellular signal many are kinases, often tyrosine kinases that phosphorylate target proteins ex: try family of neurotrophin receptors important for axon growth
effector molecule:
ion channel or additional intracellular pathways
GABA a
ionotropic receptors -pemeable to Cl- Ecl- < threshold, because [Cl-] out > [Cl-]in due to K+/Cl- co transporter -activation is hyperpolarizing -is modulated by many compounds -typically consist of 2 alpha subunits, 2 beta subunits and a gamma subunit (extracellular domain and a transmembrane domain) -inhibitory response is caused by post synaptic GABAa receptors
Define long term depression
is a form of synaptic plasticity that is associated with long lasting decrease in synaptic strength
Define long term potentiation
is a form of synaptic plasticity that is associated with long lasting increase in synaptic strength
SV2
is a membrane glycoprotein localized to synaptic vesicles and neuroendocrine secretory granules -decrease SV2A was observed in surgically removed temporal lobe tissue and postmortem hippocampal tissue fro patients with temporal lobe epilepsy
Arecoline
is an addictive CNS stimulant found in the betel nut, the seed of the Areca palm
which role does calmodulin play in the intracellular cascade triggered by Ca2+?
it binds to its downs stream targets when activated by Ca2+
why does synaptic depression occur?
it occurs because of the rapid depletion of the vesicular pool
How would an increase in external Ca concentration affect synaptic depression?
it would increase the rate of depression
which characteristic of a living hippocampus slice is critically important to its suitability as an experimental system for studying learning?
its architecture: the hippocampus can be sectioned without destroying relevant circuits
what characteristics make aplysia califonica a practical model organism for studying the nervous system?
its large neurons
what characteristics make aplysua California a practical model organism for studying the nervous system?
its large neurons
Kainate
kainic acid 5 possible subunits (GluK1, GluK2, GluK3, GluK4, and GluK5)
silent synapses
lack AMPA receptors -prevalent in development -once the postsynaptic cell is depolarized, these "silent synapses" are concerted and transmit postsynaptic electrical responses -silencing of potentiated glutamatergic synapses can result from cocaine use
Postsynaptic currents produced by AMPA glutamate receptors are _________ than those produced by other ionotrophic glutamate receptors.
larger
Postsynaptic currents produced by AMPA glutamate recpetors are ___ than those produced by other ionotopoic glutamate receptors
larger
Peptides (neuropeptides)
larger molecule transmitter post synaptic effect = excitatory and inhibitory precursor = amino acids (protein synthesis) rate limiting step = synthesis and transport removal mech = proteases type of vesicle = large dense core
How long does synaptic depression last?
lasts for only a few seconds
Ras Pathway
leads to MAPK -primarily stimulate processes responsible for neuronal differentiation
PI3 kinase pathway
leads to activation of Act kinase -primarily involved in cell survival
PLC pathway
leads to release of intracellular Ca2+ from endoplasmic reticulum and activation of PKC -primarily stimulate processes responsible for neuronal differentiation
enkephalins
leu-enkephalin met-enkephalin dynorphins dynorphin A dynorphin B
channel linked receptors
ligand gated ion channels have receptor and traducing functions as part of same molecule -ligand binding results in ion flux (but may also require other conditions) ex. ionotropic neurotransmitter receptors
The cell bodies of neurons that release norepinephrine project from what structure?
locus coeruleus
The main location of noradrenergic cell bodies in the CNS is the _____.
locus coeruleus.
LTD long tern depression
long lasting decrease in synaptic strength
(c)
long lasting hyper polarization repetitive firing mediated by autocrine 2-AG
LTP Long term Potentiation
long lasting increase in synaptic strength -discovered in the trisynaptic circuit of the hippocampus by loom and bliss (1973)
Plasticty that involves: prolong activation CREB activation - Persistent PKA activation Regulation of other downstream genes- addition of synaptic terminals is called_______
long-term plasticity
molecular mechanism of eCB-LTD (endocannabinoid long term depression
mGluR activation and increased Ca2+ leads to 2-AG synthesis via PLCbeta-DGLalpha pathway -activation of presynaptic CB1R by 2-AG inhibits adenylyl cyclase (AC), decreases cAMP levels and reduces protein Kinase A (PKA) activity -reduced PKA activity and calcineurin lead to dephospho rylation of target proteins (x) and induces persistent suppression of transmitter release
Although purinergic ionotrophic receptors are widely distributed in the CNS, their only known roles are in _______ and _______.
mechanosensation and pain
CaMKII and PKC
mediate "early" LTP (one to two hours)
learning and memory
mediated by plasticity which can endure for years
synthetic opiates
meperidine, methadone, and fentanyl are also powerful analgesics
Dopaminergic cell bodies in the VTA send projections to the nucleus accumbens and the amygdala via the _______ dopamine pathway.
mesolimbic
What type of receptor is the mAChR?
metabotrophic
muscarinic AChR
metabotrophic and mediate most of the effects of ACh in the brain -receptors spans the plasma membrane seven times -extracellular domani binds ACh in channel, causing a conformational change that permits G-protein binding -cytoplasmic domain binds to and activates G-proteins
CB1:
metabotrophic receptor, activates G-protein. enriched in brain regions associated with drug abuse (substantial nigra)
GABA b
metobotropic receptors -often due to the activation of K+ channels and blocking Ca2+ channels -assemble as heterodimers of Bq and B2 subunits -binding of GABA to the Venus flytrap domain of the B1 subunit causes this domain to close, leading to conformational changes in transmembrane domains of both subunits that permit binding of G-Proteins thereby activating intracellular signaling processes
enduring LTP
more that 2 hours and it requires protein synthesis -this late phase of LTP appears to be initiated by protein kinase A, which goes on to activate transcription factors such as CREB -CREB induces gene expression
Ca2+.calmodulin-dependent protein Kinase type II (CaMKII)
most abundant postsynaptic protein at Schaffer collateral synapse -activated by LTP stimulus -blocking CaMKII blocks LTP
glutamate
most important transmitter for normal brain function -nearly all excitatory neurons in the CNS are glutamatergic -during brain trauma, excitotoxic brain damage is caused by excessive release of glutamate -It is a nonessential amino acid that does not cross the blood Brian barrier therefore it must be synthesized in neurons from local precursors like glutamine -excitatory synapse -> glutamate which allows Na+ to enter causing depolarization
synthesis, release, and reuptake of inhibitory neurotransmitters
most inhibitory synapses use GABA or glycine -1/3 of synapses in the brain use GABA as their inhibitory neurotransmitter -high affinity transporters terminate the actions of these transmitters and return GABA or glycine to the synaptic terminal for reuse. both are loaded into synaptic vesicles via the vesicular inhibitory amino acid transporter (VIAAT)
How long are short lasting changes (short term plasticity)
msec-1-2 minutes
cAMP mediates learning and memory
mutations cause poor performance in olfactory learning tasks
Cerebellar LTD is associative
occur with coincident activation of climbing and parallel fibers -parallel fiber glutamate release activates: *AMPARs -> depolarization *mGluRs -> IP3 -> increase in [Ca2+] *mGluRs -> DAG -> PKC that eventually lead to AMPAR internalization -climbing fiber glutamate release activates: *AMPARs -> depolarization *VGCC -> increase [Ca2+] *IP3 + Ca2+ -> massive increase in [Ca2+] which eventually leads to AMPAR internalization -Note***kinase dependent LTD in cerebellum, not Phosphatase
cell-associated signaling molecules
on surface of the plasma membrane -act only on other cells in physical contact -important in neuronal development and other circumstances where physical contact between cells provides information about cellular identities ex. integrins attach to ECM, neural cell adhesion molecules (NCSMd) which influence axonal growth
AChE blockers
organophosphates, nerve gas sarin
Glutamate transporters (VGLUTs):
packages glutamate into synaptic vesicles
Aside prolonged high-frequency causes LTP?
pairing of presynaptic and postsynaptic stimulation causes LTP
which molecule is an effector directly downstream of an activated G-protein?
phospholipase C
Key features of 2-AG signaling
phospholipase hydrolyzes PI, generated diacylglycerol (DG), which is then converted to 2-AG -2-AG activates CB1R -2-AG is degraded by monoacyglycerol lipase (MGL), ABHD6, COX-2 -activation of presynaptic CB1R causes suppression of neurotransmitter release through inhibition of Ca2+ channels or some other mechanism
which neuronal mechanism most directly increases the production of catecholamine neurotransmitters?
phosphorylation of tyrosine hydroxyls
unconventional neurotranmitters: NO (nitric oxide)
post synaptic effect = excitatory and inhibitory precursor = arginine rate limiting step = nitric oxide synthesis removal mech =spontaneous oxidation type of vesicle = none
unconventional neurotransmitters: endocannabinoids
post synaptic effect = inhibits inhibition precursor = Membrane lipids rate limiting step = enzymatic modification of lipids removal mech =hydrolisis by FAAH type of vesicle = none
Which type of short-term synaptic plasticity lasts the longest?
post-tenatic potentiation
which type of short term synaptic plasticity lasts the longest?
post-tetanic potentiation
Short term plasticity involves
posttranslational modification of existing proteins
Post-Titanic potentiation (PTP):
potentiation can outlast titanic stimulus, on order of tens of seconds to minutes -arises from prolonged elevation of presynaptic calcium
CB1 type cannabinoid receptors are
presynaptic
signaling cell:
presynaptic neuron
AMPARs:
primary mediators of excitatory transmission
ATPase NSF and SNAPs:
prime synaptic vesicles for fusion by regulating the assembly of other proteins that are called SNAREs
Define habituation
process that causes the animal (or human) to become less responsive to repeated occurrences of stimulus (that preciously evoked the response). The habituation happens when no reward or punishment follows the repeated stimulation.
alpha-conotoxin:
produced by fish hunting marine cone snails, blocks each receptors
How does presynptic enhancement cause long lasting sensitization
prolong activation CREB activation - Persistent PKA activation Regulation of other downstream genes- addition of synaptic terminals
depletion of vesicles from ready-to-be released pool is attributed to
prolonged elevation presynaptic Ca2+ level following sustained synaptic activity
What will lead to increase of transmitter release?
prolonged elevation presynaptic Ca2+ level following synaptic activity
ATP (Purines)
purines = small molecule transmitter post synaptic effect = excitatory precursor = ADP rate limiting step = mitochondrial oxidative phosphororylation; glycolysis removal mech = hydrolysis to AMP and adenosine type of vesicle = small, clear
LTD in cerebellum
purkinje neurons in cerebellum receive 2 distinct types of excitatory input: -climbing fibers and parallel fibers -LTD reduces the strength of transmission at the parallel fiber synapse -implicated in coordination, acquisition, and storage of complex movement
Acetylcholinesterase (AChE)
rapidly hydrolyzes ACh into acetate and choline
habituation:
reduced response to repeated stimulus ex aplysia withdraws gills less after repeated touch siphon -transmission at the glutamatergic synapse between the sensory and motor neurons is depressed *due to presynaptic SV depletion
β-receptor antagonists help patients with generalized anxiety by _____.
reducing some of the physical symptoms associated with anxiety.
SNAPs
soluble NSF - attachment proteins
dendritic spines
specialized signaling compartments within neurons -protrusions on dendrite which form postsynaptic site of innervation -excitatory -spine shape can change over time -large surface area -diffusion limited compartment -serves as reservoirs when signaling proteins such as the downstream molecular targets of second messengers signals can be concentrated -glutamate receptors are highly concentrated on spine heads
endocannabinoid mediated retrograde control of GABA release:
stimulation of presynaptic interneuron causes release of GABA onto a postsynaptic pyramidal neuron -retrograde signals regulate GABA release at certain inhibitory synapses -depolarization elevates postsynaptic Ca2+ release of endocannibinoids from the postsynaptic cells -the stimulation of presynaptic CB1 receptors -inhibition of GABA release in response to presynaptic action (mechanism unknown)
why do we need Prolonged high frequency?
stimulation of the presynaptic terminals ensures depolarization at post synapse. This causes LTP
Properties of Long term potentiation?
strong activity of presynaptic and post synaptic neurons is required Specificity Associativity
post synaptic responses mediated by inotropic glutamate receptors
subtypes: AMPA receptors, NMDA receptors, Kainate receptors named after the agonists that activate them -most central excitatory synapses possess both AMPA and NMDA receptors. -antagonist drugs that selectively block AMPARs or NMDARs identify synaptic responses mediated by each -contribution of AMPA and NMDA receptors at the synapse between presynaptic pyramidal cell and postsynaptic interferon in the visual cortex. blocking NMDA receptors reveals a large fast EPSC mediated by AMPA receptors, while blocking AMPA receptors reveals a slower EPSC component mediated by NMDA receptors -contribution of AMPA and Kainate receptors at excitatory synapse between mossy fibers and CA3 pyramidal cells in the hippocampus. AMPA is larger and decays faster than kainate.
endocannabinoids __________ transfer release, resulting in short term depression of synaptic responses
suppress
the Ca2+ sensor for vesicle fusion is
synanaptotagmin
refer to the figure 8.1 D which statement describes the depicted phenomenon most accurately?
synaptic depression directly correlates with the amount of neurotransmitter released
_______ (underlying _____) and _______ (underlying _________) in Aplysia are due to ________
synaptic depression; habituation; increase in synaptic excitation; sensitization; presynaptic modulation
forms of chemical communication
synaptic transmission, paracrine signaling, and endocrine signaling
vesicular SNARE
synaptobrevin
plasma membrane SNAREs:
syntaxin and SNAP-25
Gamma-aminobutyric acid (GABA)
synthesized from glutamate by the enzyme glutamic acid decarboxylase, which requires pyridoxal phosphate -inhibitory synapse -> GABA which allows Cl- to enter leading to hyperpolarization.
Spike timing dependent plasticity: (STDP)
temporal relationship between pre- and postsynaptic activity determines of the amount and direction of long term synaptic plasticity -presynaptic activity precedes postsynaptic AP = LTD Postsynaptic AP follows presynaptic = LTP -STDP can provide a means of encoding information about causality. -if presynaptic neuron is activated 40 msec or less before the postsynaptic neuron, then LTP occurs -conversely, if the postsynaptic neuron is activated 40 msec or less before the presynaptic neuron, LTD occurs -if it is longer than no STDP is observed
Why would synaptic augmentation occur?
tetanic activity at the presynapse
In instrumental conditioning, the subject learns
that a particular behavior is associated with a particular consequences
function and structure of the NMDA receptor
requires glutamate -glutamate and glycine binding sites are important regions fro experimental competitive inhibition antagonists: DCKA and D-APV = blocked agonists: Glycine, Glutamate = open
cell-permeant signaling molecules
secreted -hydrophobic: cross plasma membrane to act directly on receptors that are inside the cell -often transported in blood and other extracellular fluids by binding to specific carrier proteins ex. steroid hormones (glucocorticoids, estradiol, and testosterone), thyroid hormones (thyroxin), retinoids
cell impermeant signaling molecules:
secreted -typically bind to receptors associated with the plasma membrane. -typically short lived (rapid metabolism, or because they or internalized by endocytosis once bound to their receptors ex: neurotransmitters, neurotrophic factors (encourage axon growth) , peptide hormones such as glucagon receptors span plasma, with extracellular and intracellular signaling
A group of mice is given reserpine as part of an experiment. Behaviorally, these animals would be expected to show _____.
sedation
short term sensitization:
sensory neurons excite modulatory interneurons (serotonergic) leading to potentiation of motor neurons -due to presynaptic potentiation -due to acute, PKA-dependent enhancement of sensory neurons
Which substance is a neurotransmitter that stimulates 5-HT receptors, which have been implicated in circadian rhythm, satiety, motor behavior, and emotional state regulation?
serotonin
what is the greatest advantage of the chemical signal transduction scheme?
signal amplification
Describe associativity in Long Term Potentiation
simultaneous stimulation of two pathways to one cells is causing LTP in both synaptic pathways (even if one of the pathways produce no LTP when solely stimulated). This property may be linked to associative learning (ex. classical conditioning)
short term memory
single stimulus, withdrawal reflex remains enhanced for at least an hour
Hippocampus
site of some new memory formation -can be section such that relevant circuitry is left intact
NMDAR EPSC:
slower, longer, smaller than those of AMOARs receptors
acetylcholine
small molecule transmitter postsynaptic effect = excitatory precursor = choline + acetyl CoA rate limiting step = ChAT removal mech= AChE type of vesicle = small, clear
neuropeptides:
small protein like molecules used by neurons to communicate with each other
neuropeptides:
small proteins used in signaling -vary in length from 3-36 amino acids
To which category of neurotransmitters does acetylcholine belong?
small-molecule
which category of neurotransmitters does acetylcholine belong?
small-molecule neurotransmitters
reduced levels of ________ are found in Alzheimer's patients
snynatophysin
glutamate synteses and cycling between neurons and glia:
the action of glutamate released into the synaptic cleft is terminated by uptake into surrounding glial cells ( and neurons) via excitatory amino acid transporters. within glial cells, glutamate is connected to glutamine by glutamine synthetase and released by glial cells through SN1 transporter. glutamine is taken up into nerve terminals via SAT2 transporters and converted back to glutamate by glutaminase. glutamate is then loaded into synaptic vesicles via vesicular glutamate transporters (VGLUTs) to complete the cycle
The main reason for giving albuterol via inhaler is that it reduces _____.
works quicker
the storage and release of neurotransmitters is associated with
the presynaptic terminal
Reduced exterior Ca2+ will lead to
the rate of synaptic depression is going to be greatly reduced
What happens to rate of synaptic depression and the vesicular pool when extracellular Ca2+ is lowered?
the rate of synaptic depression is going to be greatly reduced The vesicular pool is slowly depleting
Why does the function of GABA-A receptors vary among neuronal types?
there are multiple types of GABA-A receptor subunits
excitatory actions of GABA in developing brain
young neurons, intracellular Cl- concentration is controlled mainly by Na+/K=/Cl- co-transporter, which pumps Cl- into the neurons and yields a high [Cl-]in -in this case Ecl is more positive than the resting potential thus making GABA excitatory
Which toxins blocks neuromuscular transmission by irreversibly binding to nictotinic acetylcholine receptors, thus preventing acetylcholine from opening postsynaptic ion channels?
α-bungarotoxin
which statement about silent synapses is true?
they contain both NMDA and AMPA receptors
Monoamine oxidase inhibitors are sometimes used in the treatment of Parkinson's disease. What is their mechanism of action?
they inhibit the breakdown of dopamine
monoamines oxidase inhibitors are sometimes used in the treatment of Parkinson's disease. what is their mechanism of action?
they inhibit the breakdown of dopamine.
hetrotrimeric G-protein
three distinct classes of subunits (alpha beta and gamma) -alpha subunit binds to GDP, exchanged for GTP -GTP-bound alpha subunit activates effector molecules -alpha subunit dissociates from beta gamma complex -GTP bound alpha subunit activates effector molecules -GTP hydrolysis to GTP terminates signal
nuclear receptors
transcriptional activators upon ligand binding ex: thyroid hormone receptor
the catalytic domain of a protein kinase
transfers a phosphate group to the relevant amino acid of the target protein.
Glutaminase:
transforms glutamine to glutamate
System N transporter 1 (SN1):
transport glutamate out of the glial cells
Levetiracetam:
treats epilepsy targets synaptic vesicle bound SV2, although its mechanism of action is not yet fully understood
true or false proteins essential for synaptic vesicle release and recycling are potential therapeutic targets for diseases of the brain.
true
true or false: endocannabinoids can influence neuronal excitability in a manner that is independent of CB1R`
true
true or false: glial cells contribute to endocannabinoid signaling
true
true or false: proteins essential for synaptic vesicle release and recycling are potential therapeutic targets for diseases of the brain
true
What is the common precursor of all catecholamines?
tyrosine
what is a common precursor of all catecholamines?
tyrosine
biosynthetic pathway for catecholamine neurotransmitters
tyrosine + tyrosine hydroxylase = DOPA DOPA + dopa decarboxylase = Dopamine Dopamine + Dopamine - beta- hydroxylase = norepinephrine norepinephrine + phenyl ethanol-amine-N-menthyl-transferase = Epinephrine
TrkA:
tyrosine kinase receptor for NGF -binding causes TrkA to dimerize -each subunit phosphorylates the partner subunit -P-TrkA triggers the raw cascade
immediate early genes:
unregulated in response to neural activity ex: c-fos (transcription factor)
At which point in the glutamate-glutamine cycle is postsynaptic glutamate action terminated rapidly?
uptake of glutamate by presynaptic terminal and glial cells
presynaptic vesicle fusion machinery
vesicle bound proteins interact with cytosolic modulators and presynaptic membrane bound target proteins -SNARE complex forms the central mechanism for vesicle fusion by bringing vesicles and presynaptic membrane together -many other molecular players are modulatory
The _______ is responsible for packaging molecules of dopamine into vesicles for release.
vesicular monoamine transporter
Three classes of cell signaling molecules.
(A) Cell-impermeant molecules:, such as neurotransmitters, cannot readily traverse the plasma membrane of the target cell and must bind to the extracellular portion of transmembrane receptor proteins. (B) Cell-permeant molecules: are able to cross the plasma membrane and bind to receptors in the cytoplasm or nucleus of target cells. (C) Cell-associated molecules: are presented on the extracellular surface of the plasma membrane. These signals activate receptors on target cells only if they are directly adjacent to the signaling cell.
Synthesis, release, and reuptake of the inhibitory neurotransmitters GABA and glycine.
(A) GABA is synthesized from glutamate by the enzyme glutamic acid decarboxylase, which requires pyridoxal phosphate. (B) Glycine can be synthesized by several metabolic pathways; in the brain, the major precursor is serine. High-affinity transporters terminate the actions of these transmitters and return GABA or glycine to the synaptic terminals for reuse, with both transmitters being loaded into synaptic vesicles via the vesicular inhibitory amino acid transporter (VIAAT).
Types of GTP-binding proteins
(A) Heterotrimeric G-proteins: consist of three distinct subunits (α, β, and γ). Receptor activation causes the binding of the G-protein and the α subunit to exchange GDP for GTP, leading to a dissociation of the α and βγ subunits. The biological actions of these G-proteins are terminated by hydrolysis of GTP, which is enhanced by GTPase-activating (GAP) proteins. (B) Monomeric G-proteins: use similar mechanisms to relay signals from activated cell surface receptors to intracellular targets. The biological actions of these G-proteins depends on binding of GTP, which is activated by guanine nucleotide exchange factors (GEFs) that bind to the receptor in association with adaptor proteins, and their activity is terminated by hydrolysis of GTP, which is also regulated by GAP proteins.
Synthesis of histamine and serotonin.
(A) Histamine is synthesized from the amino acid histidine. (B) Serotonin is derived from the amino acid tryptophan by a two-step process that requires the enzymes tryptophan-5-hydroxylase and a decarboxylase.
Activation of protein kinases.
(A) In the inactive state (left), the catalytic subunits of PKA are inhibited by the regulatory subunits. Binding of cAMP to the regulatory subunits relieves the inhibition and frees the catalytic subunits to phosphorylate their targets. Black lines indicate flexible structures that connect parts of the regulatory subunit. (B) CaMKII is a large wheel-shaped structure comprising 12 subunits, each with a catalytic (tan/yellow) and a regulatory (blue) domain, held together by a central association domain (green). Binding of Ca2+/calmodulin to the regulatory domain allows the catalytic domain to extend and phosphorylate its substrates. (C) Binding of Ca2+ allows lipid-binding domains of PKC (blue) to insert into the plasma membrane and bind to DAG and other membrane lipids. This change in structure and location displaces the regulatory domain (blue) allows the catalytic domain of PKC (yellow) to phosphorylate its substrates. Black lines indicate flexible structures that connect the various domains of PKC. (D) Activation of MAPK is caused by phosphorylation of an activation loop (yellow) by upstream kinases. Phosphorylation of the activation loop allows the catalytic domain of MAPK to assume its active conformation and phosphorylate downstream targets.
Types of protein phosphatases.
(A) Structure of PP1, consisting of a catalytic subunit (red) bound to spinophilin (blue), a regulatory subunit found in dendritic spines. (B) PP2A is a trimeric enzyme that has a scaffold subunit (yellow), in addition to the catalytic (red) and regulatory (blue) subunits common to other phosphatases. (C) The activity of PP2B, or calcineurin, is regulated by Ca2+/calmodulin. In the absence of Ca2+/calmodulin (left), part of the regulatory subunit blocks the active site of the catalytic subunit, preventing phosphatase activity. Binding of Ca2+/calmodulin to the regulatory subunit relieves this blockade, allowing PP2B to dephosphorylate its substrate proteins.
diphenhydramine
(Benadryl, a histamine receptor antagonist): sedative side effects caused by crossing blood brain barrier
ATPase NSF
(NEM-sensitive fusion protein)
diversity of functional roles of endocannabinoids
(a) eCB activates presynaptic CB1R and suppress LTP (b, b') eCBs activated CB1R of nearby interneurons and activate K+ channels, decrease in firing rate, influences activity of target neurons (b') (c) long lasting hyperpolarization repetitive firing mediated by autocrine 2-AG (d, d') eCBs activated astrocytic CB1R which leads to increase in Ca2+ levels which leads to glutamate release, where it potentiates the excitatory transmission via presynaptic group 1 mGluRs (e) at certain types of synapses, synaptic stimulation induces a novel type of postsynaptic long term depression (LTD), which is CB1R independent, TRPV1 dependent and anandamide dependent
morphine
(not endogenous) activates opined receptors
List the steps of the mechanism underlying long term depression
* prolonged low frequency stimulation lead to weakening of synapses * Slow and low rises in Ca2+ leads to depression *Activation of Ca2+ dependent phosphatases *Internalization of AMPA receptors
glutamate-glutamine cycle: neuronal glutamate syntesis
-System A transporter 2 (SAT2): brings glutamine into presynaptic -glutaminase transforms glutamine to glutamate (glucose can also be metabolized by transamination of 2-oxoglutarate, an intermediate of tricarboxylic acid (Krebs) cycle) -glutamate transporter (VGLUTs) package glutamate into synaptic vesicles
clinical application epilepsy:
-atypical neuronal activity generates plastic changes in cortical circuitry that are critical to the pathogenesis of the disease -seizures results from hyper-excitability of certain neurons -therapeutic strategies: *increase GABA inhibitory synapses *decrease Ads by voltage gated Na+ channels
Metabotropic Glutamate receptors (mGluRs)
-cause slower postsynaptic response than inotropic receptors -wide variety of function -formed by dimers of subunits which each have seven transmembrane domains. consist of a pair of identical subunits, each containing a Venus flytrap domain, cysteine-rich linker domain, a transmembrane domain consisting of canonical seven membrane-spanning helices -binding of glutamate causes Venus flytrap domains to rotate and bind to G-proteins leading to intracellular signaling. -class I: mGlu1, mGlu5 -class II: mGlu2, mGlu3 -class III: mGlu4, mGlu6, mGlu7, mGlu8
3 classes of cell signaling
-cell impermeant signaling molecules -cell-permeant signaling molecules -cell-associated signaling molecules
Which conditions must be met to induce LTP?
-glutamate must open the postsynaptic AMPA receptors -the postsynaptic membrane must be depolarized for a period of time -Mg block must be expelled from NMDA receptors to allow Ca influx
subsequent expression (after induction) of LTP
-relies on dynamic chances in AMPA receptors -LTP causes an increase in glutamate response of dendritic spine dues to an increase in the number of AMPA receptors on the spine membrane -increase in the number of AMPA receptors increases the response of the postsynaptic cell to release glutamate
15. Which property of LTP underlies Pavlovian conditioning? a. Requirement for coincident activation of pre- and postsynaptic neurons b. Specificity of input c. Associativity d. Complementarity e. Transience Answer: c
. Associativity
. Which statement about the mechanisms underlying hippocampal LTP induction is false? a. An influx of calcium triggers two or more intracellular processes in the postsynaptic dendritic spine. b. Calcium may enhance transmitter release from the presynaptic terminal. c. Calcium may activate Ca2+/calmodulin-dependent protein kinase type II (CaMKII), which then autophosphorylates, leading to a long-term "on" state. d. Calcium may activate a signaling cascade that causes the insertion of glutamate receptors into the postsynaptic membrane. e. Calcium decreases a resting leak current of sodium so that the postsynaptic cell is closer to threshold and therefore fires more easily. Answer: e
. Calcium decreases a resting leak current of sodium so that the postsynaptic cell is closer to threshold and therefore fires more easily.
. Which Drosophila melanogaster genotype is associated with the worst performance in an olfactory learning task? a. Wild type b. Dunce mutant c. Rutabaga mutant d. Dunce, rutabaga double mutant e. The performance of all phenotypes is comparable. Answer: d
. Dunce, rutabaga double mutant
What does LTP cause
1. Morphological changes in Dendrite spines 2. Intracellular Ca 2+ increase 3. Activation of CAM KII (important for regulation of synapse and vesticular release) 4. Number of AMPA receptors increase (depending on number of Ca 2+ that is coming in)
Why is short term presynapse important?
1. Vesicular release at chemical synapse depend on voltage gated calcium channel due to depolarization of the membrane 2. Process of release and process of vesicular recycling is high regulated by several proteins at the presynapse. This process is depending on the presence of calcium. Calcium is necessary for interaction of synaptotagmin with SNARE complex Important for the function of synapsin (holds vessicles in reserve pool), it activates CAMKII which allows synapsin to move vessicles and cock them into the membrane. Movement of vesicles is regulated by snapsin which is regulated by calcium depending kinase
What is the smallest subunit composition of a typical GABA-A receptor?
2 alphas, 2 betas, and a gamma
What is the subunit composition of a typical GABAa receptor?
2alpha, 2beta and 1 gamma
How long are long lasting changes (long term plasticity)
30 minutes or longer
The amount of time for long term plasticity
30 minutes or longer
small clear core vesicles:
40 to 60 nm, enclose small-molecule neurotransmitters
serotonin metabotropic receptors
5-HT, LSD binds to the 5-HT binding site
refer to the figure 8.1 B at which time interval would the postsynaptic membrane potential of the second stimulus be greatest?
8 ms
At which time interval would the postsynaptic membrane potential of the second stimulus be greatest?
8 seconds
large dense-core vesicles
90 to 250 nm in diameter, appear electron-dense in electron micrographs, enclose neuropeptides
1. Define the term "synaptic plasticity."
: It is the ability of synapses to change in strength.
DG
= diacylglycerol
Parkinson's disease:
A disorder of the central nervous system that affects movement, often including tremors. dopaminergic neurons of the substantial migration degenerate, motor dysfunction
mossy fiber
A fiber connecting a neuron in the pons to the granule cells of the cerebellum
Mechanisms underlying LTD.
A low-amplitude rise in Ca2+ concentration in the postsynaptic CA1 neuron activates postsynaptic protein phosphatases, which cause internalization of postsynaptic AMPA receptors, thereby decreasing the sensitivity to glutamate released from the Schaffer collateral terminals.
Imprinting
A very rapid learning that occurs during a short window (critical period) after birth and establishes long-lasting behavioral responses to a specific object or individual.
acetylcholine metabolism in choleric nerve terminals
AChE rapidly hydrolyzes ACh into acetate and choline choline is recycled back into nerve terminals for ACH resynthesis
Functional synapse (mature syanpses) have _____ receptors
AMPA and NMDA Receptors
At resting potential, what receptors are able to permate ion and affect membrane potential?
AMPA receptor
coincidence detection:
APs in presynaptic Schaffer collaterals which would not normally yield LTP can be paired with postsynaptic depolarization to give LTP
Which pathology leads to an increased risk of Alzheimer's disease?
Accumulation of the Aβ42 peptide
Acetylcholine synthesis
Acetyl CoA is derived from pyruvate generated by glycolysis choline is transported into the terminal via an Na+ dependent co transporter (ChT) Acetylcholine is loaded into synaptic vesicles via a vesicular transporter (VAChT)
Which process does not take place during LTD?
Activation of protein kinase
Why are adrenergic agonists and antagonists important in the treatment of many nonpsychiatric medical conditions?
Adrenergic receptors are found on a wide variety of peripheral organs.
Which is an example of phylogenetic memory?
An infant monkey being frightened of snakes
What did Edward Thorndike claim
Animals learn gradually and not by insight
Why is it thought that Ca2+ levels might be involved in spike timing-dependent plasticity (STDP)?
Answer: If postsynaptic Ca2+ levels are high (as they are when presynaptic activity precedes postsynaptic potential), LTP occurs. If postsynaptic Ca2+ levels are low (as they are when postsynaptic potential precedes presynaptic activity), LTD occurs.
Genetics and other molecules that play a role in AD
ApoE gene, early family onset. presence of beta-amyloid plaques and neurofibrillary tangles (NFTs)
Which property of LTP underlies Pavlovian conditioning?
Associativity
What is happening in the experiment with elementary forms of behavior plasticity in Aplysia from Trial 1 to Trial 13
At trial 1, there is gill contraction, by trial 6, the gill contraction is decreased, and by trial 13, there is little magnitiude of gill contraction
Give an example of classical conditioning
Blowing a whistle a few seconds before food will cause a dog to salivate when he hears the sound of the whistle
agonists of CB1 include
Both anandamide, and 2-arachidonylglycerol (2-AG)
In what way are GABA and glutamate similar in the adult brain?
Both are both common in the nervous system
Which statement about the structural changes that occur in the brain during healthy aging is accurate?
Brain weight decreases due to a decline in the number of synapses
Why is the second postsynaptic potential of synaptic facilitation larger then the first postsynaptic potential?
Build up of calcium at the presynapse and with second potential arriving with less then 50 milisecond, the second postsynaptic action potential is larger due to the build up of calcium.
What causes synaptic facilitation?
Buildup of Ca in the presynaptic terminal
Cholera toxin locks the Gs subunit into an active state, in that GTP is bound and cannot be hydrolyzed back to GDP to turn off the subunit. What effect will cholera toxin have in the cell? a) the Gs subunit will more strongly inhibit adenylyl cyclase b) activated adenylyl cyclase will lead to decreased cyclic AMP levels c) inhibited adenylyl cylcase will lead to increased cyclic AMP levels d) increased cyclic AMP levels will lead to increased protein kinase A activation e) Decreased cyclic AMP levels will lead to decreased protein kinase A activation
D
Most enzyme-linked receptors affect the function of the target cell by a) generating an action potential b) catalyzing synthesis of hormones in the cytoplasm c) facilitating the assembly of the cytoskeleton d) phosphorylating intracellular target proteins e) dimerizing
D
Schaffer collateral
CA1 synapses induced by tetany stimulation and can last a year
modulation of presynaptic CB1R signaling
CB1R is inhibited by presynaptic activity -CB1R suppresses transmitter release through an undetermined mechanism which is dependent on Kainate receptors -presynaptic A1 adenosine receptor (A1R) inhibits the CB1R function. (note that CB1R and A1R are both Gi/o-coupled receptors and may use overlapping sets of G alpha alpha subunits.
Which protein facilities the late phase of LTP?
CREB
which protein most directly facilitates the late phase of LTP
CREB
Activation of _____ and _____ is called long-term plasticity
CREB, C-Fos
What binds to synaptotagmin?
Ca 2+
What is step 3 of phase 1 of Long term Potentiation (LTP)
Ca 2+ activates CaMKII
What catalyzes membrane fusion
Ca 2+ bound synaptotagmin
What is the intermediate consequence of mG blockade removal from the NMDA receptors?
Ca influx into the postsynaptic terminal
What enters through the opening of the NMDA receptor channel?
Ca2+
which second messenger originates from both extracellular and intracellular compartments?
Ca2+
neuronal second messengers
Ca2+ Cyclic AMP Cyclic GMP IP3 Diacylglycerol
CaMKII activity increases in the dendrite of a CA1 pyramidal neuron during LTP
Ca2+ activates complex postsynaptic signal transduction cascades -CaMKII and PKC phosphorylate downstream targets: AMPARPKCs and other targets, that collectively facilitate delivery of AMPA receptors to the synapse
Potentiation
Ca2+ activates presynaptic protein kinases that go on to phosphorylate substrates (such as synapsin) that regulate transmitter release over a timescale of tens of seconds to minutes -repeated synaptic activity increases the amount of transmitter released
calbindin:
Ca2+ buffer, blunts response
the release of endocannabinoids from post synaptic neurons can be induced by
Ca2+ elevation
LTP at the Schaffer collateral-CA1 synapse
Ca2+ imflux via NMDRs activates synaptotagmins and kinases -AMPARs inserted into synapse -other forms of LTP are observed at other synapses and may rely on different signaling mechanisms.
vesicles fusion and neurotransmitters release occurs in a precise time locked manner which depends on
Ca2+ release
augmentation:
Ca2+ unregulated presynaptic SNARE-regulatory protein muncher's-13 and increases EPSCs over the course of a few seconds -0.1[Ca2+]: lowest Ca2+, SV depletion, but Ca2+ accumulates leading to augmentation
What is step 4 of phase 1 of Long term Potentiation (LTP)
CaMKII phoshporylation of proteins, including AMPA receptors
What results in LTP
Calcium going in due to depolarization allowing NMDA receptors to allow Ca2+ in.
Which second messenger is involved in postsynaptic depresion
Calcium, DAG and IP3
Where are long-term declarative memories stored?
Cerebral cortex
Which process differentiates long-term from short-term sensitization?
Changes in gene expression
When a GABAa ionotropic receptor is stimulated by GABA in a developing neuron, which ions flow through its channel, and what effect does this have on the postsynaptic cell?
Cl-, which depolarized the post synaptic cell.
When a GABA-A ionotrophic receptor is stimulated by GABA in a developing neuron, which ion flows through the channel? What effect does it have?
Cl-; it depolarizes the postsynaptic cell
_______ and _______ exert their pharmacological effects by blocking monoamine reuptake.
Cocaine; tricyclic antidepressants
How to help AD??
Come up with non invasive diagnostic test Understand pathology of the disease
During a learning test, a subject wears a small device on their finger that elicits a painful shock. When this occurs, the subject's heart rate increases slightly, but significantly. As part of the test, the shock is consistently paired with a red light. After a number of pairings, the person responds with an elevated heart rate to the red light alone. In this example, which term best describes the red light?
Conditioned stimulus
Instrumental conditioning
Conditioning that involves association of a response with a meaning stimulus (reward) It is called trial-and error learning because the animal is free to try various responses before finding the one that is rewarded. The subject learns that a particular behavior is associated with a particular consequences
Tactile information from the face to the CNS follows which pathway?
Cutaneuous receptors, CN V, trigeminal brainstem complex, VPM of thalamus, contralateral cortex
. Which protein facilitates the late phase of LTP? a. Synaptotagmin b. CaMKII c. CREB d. PKC e. Clathrin Answer: c
c. CREB
Categories of cellular receptors
-A) Cell-impermeant signaling molecules can bind to and activate channel-linked receptors. 1. signal binds 2. channel opens 3. ions flow across membrane -B) enzyme-linked receptors. 1. signal binds 2. enzyme activated 3. enzyme generates activated effector -C) G-protein-coupled receptors. 1. signal binds 2. G-protein binds 3. G-protein activated -D) Cell-permeant signaling molecules activate intracellular receptors. 1. signal binds 2. activated receptor regulates transcription
synthesis, release and reuptake of GABA
-GAD catalyzes the conversion of glutamate to GABA -GABA is metabolized in TCA cycle for ATP production -GABA can be broken down to game- hydroxybutyrate (roofies), by competing with GABA degradation.
Which statement about LTP is false? a. LTP involves an enhancement in synaptic efficacy that can last for hours, days, weeks or even longer. b. If one synapse (A) is very strongly stimulated (sufficient to cause LTP), and another nearby synapse (B) on the same dendrite is weakly stimulated at the same time, then the second synapse (B) will also show LTP. c. If one synapse (A) is very strongly stimulated (sufficient to cause LTP), and a nearby synapse (B) on the same cell is weakly stimulated a few seconds later, then the second synapse (B) will also show LTP. d. The requirement for coincident pre- and postsynaptic activity was predicted by Donald Hebb in 1949. e. Hippocampal LTP was first reported by Bliss and Lomo about 1970. Answer: c
. If one synapse (A) is very strongly stimulated (sufficient to cause LTP), and a nearby synapse (B) on the same cell is weakly stimulated a few seconds later, then the second synapse (B) will also show LTP.
Which statement about kindling is true? a. Its effect is reversible. b. Its effect is long-lasting. c. It is based on use of a single, weak stimulus to change the excitability of the brain. d. It is used to treat epilepsy. e. It is used to diagnose epilepsy. Answer: b
. Its effect is long-lasting.
. A researcher is trying to study synaptic transmission in a glutamatergic hippocampal neuron. She is tasked with measuring calcium flow in the postsynaptic hippocampal neuron after either low or high intensity stimulation to the presynaptic neuron. During the experiment, she measures calcium influx after both low and high stimulation. Which statement best describes the error she made? a. She forgot to add magnesium to the extracellular solution b. She forgot to add calcium to the extracellular solution c. She forgot to add sodium to the extracellular solution d. She forgot to add potassium to the extracellular solution e. She completed all steps correctly. Answer: a
. She forgot to add magnesium to the extracellular solution
19. Which observation would demonstrate the spike timing-dependent plasticity of synapses? a. Whether or not LTP occurs is dependent on the specific temporal pattern of action potentials. b. LTP occurs whenever an action potential precedes an EPSP. c. LTD occurs whenever an action potential follows an EPSP. d. Switching the relative timing of action potential and EPSP by as little as 20 ms can switch the response from LTD to LTP, or vice-versa. e. A rhythmic pattern of spike-EPSP-spike-EPSP, at 40 ms intervals, produces maximal LTP. Answer: d
. Switching the relative timing of action potential and EPSP by as little as 20 ms can switch the response from LTD to LTP, or vice-versa.
Mechanism of presynaptic enhancement
1. Serotonin GPCR activation 2. cAMP -activation of Pka 3. Proteins (K+ channels) phosphorylation 4. Presynaptic Ca 2+ increase 5. More vesicles are fused
chemical signaling require
1. a molecular signal that transmits information from one cell to another 2. a receptor molecule that transduce the information provided by the signal 3. an effector molecule that mediates the cellular response
vesicle recycling following endocytosis
1. adaptor proteins (AP-2, AP-180) connect clathrin to vesicular membrane 2. clathrin triskelia assembler into coat, curving membrane to form coated pit 3. assemble clathrin cage constricts lipid stalk connecting two membranes 4. dynamin ring forms and pinches off lipid stalk 5. coated vesicle is translocated by actin filaments 6. Hsc70 and auxiliary uncut vesicle
regulation of tyrosine hydroxylase by protein phosphorylation
1. neuronal activity (AP) 2. causes influx of Ca2+ 3. the resultant rise in intracellular Ca2+ concentration activates protein Kinases 4. which phosphorylates tyrosine hydroxylase 5. stimulating catecholamine synthesis 6. this increased synthesis in turn increases the release of catecholamines 7. and enhances the postsynaptic response produced by the synapse
. What might LTP and epilepsy have in common?
: Long-lasting or even permanent changes in neuronal circuitry underlie both LTP and epilepsy.
. Define long-term potentiation (LTP). Draw a diagram that shows how LTP is obtained experimentally in CA1 of the hippocampus.
: Long-term potentiation represents a long-lasting increase in synaptic strength.
What is the synaptic basis for short-term sensitization in Aplysia?
: Modulatory interneurons strengthen synaptic transmission in the gill withdrawal circuit, that is, the synapses between the sensory and motor neurons of the siphon.
Which type of somatosensory afferents transmit touch mechanoreceptors to the CNS?
A-beta
Which component of the musculoskeletal system is responsible for force-production?
Extrafusal muscle fiber
Which is not an aspect of long-term memory?
The use of sensory-modality specific "memory registers"
Define synaptic facilitation
Increase in synaptic strength caused by elevation of presynaptic calcium concentration that, in turn, facilitates vesicular transmitter release. Facilitation occurs when more than 1 action potential arrives to presynaptic terminal within miliseconds. Rapid increase in synaptic strength that occurs when more than one action potentials arrive to presynaptic terminals within milliseconds
What is the mechanism of LTP expression?
Increase the number of postsynaptic AMPA receptors.
Which perception is an example of hyperalgesia?
Increased sensitivity to temperature after sunburn
What is the mechanism of organophosphate theory?
Inhibition of acetylcholinesterase
An electrode is used to stimulate a presynaptic nerve that synapses in the dentate gyrus (DG) of the hippocampus. Postsynaptic recordings are measured in the DG neurons. First a weak stimulus (stimulus A) is applied, and then a strong stimulus (stimulus B). If a second weak stimulus (stimulus C) is applied after the strong stimulus, which result would you expect? a. The postsynaptic response to the second weak stimulus (C) will be higher than the response to the strong stimulus (B). b. The postsynaptic response to the second weak stimulus (C) will be lower than the response to the first weak stimulus (A). c. The postsynaptic response to the second weak stimulus (C) will be equal to the response to the first weak stimulus (A). d. The postsynaptic response to the second weak stimulus (C) will be equal to the response to the strong stimulus (B). e. The postsynaptic response to the second weak stimulus (C) will be higher than the response to the first weak stimulus (A). Answer: e
The postsynaptic response to the second weak stimulus (C) will be higher than the response to the first weak stimulus (A).
Repeated stimulation of the siphon results in habituation. Which synaptic change occurs during habituation?
The synapse between the sensory and motor neuron is depressed.
The function of which synapses is altered during sensitization?
The synapse between the sensory neuron of the siphon and the motor neuron
Acetylcholine metabolism in cholinergic nerve terminals.
The synthesis of acetylcholine from choline and acetyl CoA requires choline acetyltransferase. Acetyl CoA is derived from pyruvate generated by glycolysis, while choline is transported into the terminals via an Na+-dependent co-transporter (ChT). Acetylcholine is loaded into synaptic vesicles via a vesicular transporter (VAChT). After release, acetylcholine is rapidly metabolized by acetylcholinesterase, and choline is transported back into the terminal via the ChT.
Which statement about silent synapses is true?
The transit information at resting membrane potential
Which structure contributes to the sensory-discriminative aspect of pain?
Ventral posterior medial and lateral nuclei of the thalamus
Is it possible for an innocuous stimulus, such as touch, to evoke a sensation of pain?
Yes, it occurs by means of central sensitization.
GABA is inhibitory when
[Cl-]out > [Cl-]in
At which time interval would the postsynaptic membrane potential of the second stimulus be greatest? a. 8 ms b. 15 ms c. 20 ms d. 30 ms e. 50 ms
a, 8ms
. Which process does not take place during LTD? a. Activation of protein kinases b. Activation of protein phosphatases c. Activation of PKC d. Activation of clathrin e. Activation of synaptotagmin Answer: a
a. Activation of protein kinases
1. What causes synaptic facilitation? a. Buildup of Ca2+ in the presynaptic terminal b. Release of greater than usual number of synaptic vesicles c. Release of synaptic vesicles loaded with extra neurotransmitter d. Activation of synaptotagmin 7 by means of phosphorylation e. Stronger binding of Ca2+ to synaptotagmin 7
a. Buildup of Ca2+ in the presynaptic terminal
. What is the immediate consequence of Mg2+ blockade removal from the NMDA receptors? a. Ca2+ influx into the presynaptic terminal b. Ca2+ influx into the postsynaptic terminal c. Na+ influx into the postsynaptic terminal d. Postsynaptic EPSP e. Glutamate binding to its receptors Answer: b
b. Ca2+ influx into the postsynaptic terminal
Which process differentiates long-term from short-term sensitization? a. Synaptic transmission between the facilitatory and sensory neurons b. Changes in gene expression c. PKA activation d. Production of cAMP e. Changes in the synapses between the sensory and motor neurons Answer: b
b. Changes in gene expression
. What is the mechanism of LTP expression? a. Increase in the number of postsynaptic NMDA receptors b. Increase in the number of postsynaptic AMPA receptors c. Increase in the number of presynaptic AMPA receptors d. Increase in the intracellular level of synaptotagmins e. Decrease in the level of glutamate released into the synaptic cleft Answer: b
b. Increase in the number of postsynaptic AMPA receptors
endocannabinoids are involved in
both: short term and long term depression
endocannabinoids are involved in
both: short term depression and long term depression
System A transporter 2 (SAT2):
brings glutamine into presynaptic
what causes synaptic facilitation?
buildup of Ca2+ in the presynaptic teminal
what causes synaptic facilitation?
buildup of Ca2+ in the presynaptic terminal
neurotoxins that act on nAChRs
bungarotoxin, conotoxin, arecoline
26. At which time interval between pre- and postsynaptic activity would STDP occur? a. 20 ms, but only if presynaptic activity occurs before postsynaptic activity b. 30 ms, but only if postsynaptic activity occurs before presynaptic activity c. 40 ms, regardless of whether pre- or postsynaptic activity occurs first d. 10-100 ms, regardless of whether pre- or postsynaptic activity occurs first e. 40-100 ms, regardless of whether pre- or postsynaptic activity occurs first Answer: c
c. 40 ms, regardless of whether pre- or postsynaptic activity occurs first
Define synaptic depression
decrease in synaptic strength (postsynaptic response) caused by prolong elevation of presynaptic calcium concentration that, in turn, leads to depletion of ready-to-be released pool of synaptic vessicles. It is decrease in synaptic stregnth during sustained synaptic activity, that lasts for only a few seconds
the main psychoactive component of marijuana is
delta 9 tetrahydrocannabinol (THC)
With Ca2+ entering through the opening of the NMDA receptor channel within _______ triggers _____.
dendritic spines LTP
PP2B
dephospho rylation of AMPA type glutamate receptors may cause long term depression of hippocampal synapses
What type of receptor has two binding sites, both of which must be bound by ACh in order to activate it?
nAChR
fast transmission example:
neuromuscular junctions allow a person to respond to rapidly changing cues, such as the avoiding a swerving car
Unconventional neurotransmitters transmit signals between ________.
neurons
receptors
neurotransmitter receptor
signal
neurotransmitters
Nerve growth factor (NGF)
neurotrophin family of growth factors required for differentation, survival, and synaptic connectivity
The dopamine pathway most important for regulating movement is the _______ pathway.
nigrostriatal
When NMDA membrane is hyperpolarized, even with glutmate bind to membrane, there is
no opening of channels
Ras
regulates cell differentiation and proliferation -viral form is defective, causing uncontrolled cell proliferation that leads to tumors -involved in synaptic potentiation
Serotonin (5-HT) or 5-hydroxytryptamine
regulates sleep and wakefulness serotonin pathways are target treatments of depression and anxiety synthesis pathway: tryptophan + tryptophan-5-hydroxylase yields 5-hydroxytryptophan. 5-hydroxytryptophan + aromatic l-amino acid decarboxylase yeilds serotonin
PFs: parallel fiber synapses
release glutamate *activates both AMPA type and metobotrophic receptors Metobotrophic produce IP3 and DAG in the purkinje cell. -climbing fiber depolarizes membrane potential to open Ca2+ channels. -increased Ca2+ levels associated with activity of climbing fiber synapses, the IP3 causes Ca2+ to be released from the ER, while Ca2+ and DAG together activate protein Kinase C -AMPARs cause EPSC -mGluRs receptors stimulate IP3 and DAG, but not enough to open IP3 receptors or to stimulate PKC -together these signals change the properties of AMPA receptors to produce long term depression (LTD results from fewer AMPA receptors)
neurotransmitter:
released at the end of a nerve fiber by the arrival of a nerve impulse
When NMDA membrane is Depolarized, it causes
removal of Mg2+ and opening of the channel.
Excitatory amino acid transporters (EAATs)
remove glutamate from the synaptic cleft -family of five different Na+ dependent glutamate co transporters -some in glial cells others in presynaptic terminals
long term memory
repeated pairing, reflex endures for days
Neurons in the CNS that release epinephrine regulate which function?
respiration
endocannabinoids:
retrograde signals that regulate GABA release t certain inhibitory synapses endocannabinoid receptor antagonist = rimonabant
synapsin
reversibly binds to synaptic vesicles, may keep these vesicles tethered in reserve pool by cross-linking vesicles
kainate receptor
role is less well defines
Precursors of peptide neurotransmitters are synthesized in the _____ and packaged into vesicles in the ______.
rough ER; trans-Golgi network
precursors of peptide neurotransmitters are synthesized in the _____ and packaged into vesicles in the _______.
rough endoplasmic reticulum; trans-golgi network
phosphorylation:
the addition of phosphate groups -is the post translational modification that rapidly and reversibly changes protein function
short-term plasticity at the NMJ
the effect of each mechanism is seen with the timescale of its action -Ca2+ accumulation gives rise to: *facilitation via synaptotagmin 7 activation *augmentation via muni-18 activation *depression via SC depletion *potentiation via synapsin phosphorylation
mechanisms responsible for long lasting synaptic transmission during LTP
the late component of LTP is a result of PKA activating the transcriptional regulator CREB, Which turns on expression of several genes that produce long lasting changes in PKA activity and synapse structure. -most of these newly synthesized proteins required for Late phase of LTP have not yet been identified -include other transcriptional regulators, protein kinases, and AMPA receptors -Late LTP is associated with dendritic spine enlargement
associative learning
the selective enhancement of conjointly activated sets of synaptic inputs is cellular analog of associative learning such as classical (pavlovian) conditioning
refer to the figure 8.4 A repeated stimulation of the siphon results in habituation. which synaptic change occurs during habituation?
the synapse between the sensory and the motor neurons is depressed
