NSC 4352 Final

Microtubules are organized in a + and - orientation with:

+ end at ends of axons and the - end facing the nucleus

40. In which stage of the synaptic vesicular cycle are vesicles coated in clathrin?

Endocytosis

30. At the end of vesicular fusion, there are proteins that aid in recycling. One of these proteins is called clathrin. What is its function?

Form coated pits around newly forming vesicles

Increasing intensity and duration of a stimulus will increase action potential ___________, but its _____________ remains the same.

Frequency, Amplitude

Which type of glial cell increases the conduction velocity of action potentials in the peripheral nervous system by promoting saltatory conduction?

Schwann cells

In Aplysia when touching of the siphon is paired repeatedly with a shock applied to the tail this leads to a form a long term plasticity called

Sensitization

Most kinases in the human or other mammal genomes are ______ kinases

Serine and threonine

Antidepressant drugs primarily act on the _____ system

Serotonergic

What prevents the action potential from propagating backwards?

Sodium channel inactivation

Gαs proteins produce which of the following cellular responses

Stimulation of adenylyl cyclase and stimulation of cAMP accumulation

25. Classical neurotransmitters such as GABA and glutamate are:

Synthesized in the presynaptic terminal

Each ion channel has a specific number of transmembrane domains and protein subunits that are needed to form a functional channel. How many subunits and transmembrane domains does a voltage gated Ca++ channel have?

1, 24

Voltage gated sodium channels have how many transmembrane domains per individual protein?

24

In hippocampus or cortex, LTD can be induced by stimulation at ___ Hz whereas LTP might be induced by stimulation at ___ Hz.

3, 50

There are approximately _____ kinases in the human genome

500

The ion channel receptor for serotonin is called

5HT3

G-protein coupled receptors (GPCRs) have how many transmembrane domains

7

The GPCR cycle is terminated when Gα subunit

Hydrolyzes GTP to GDP and rebinds βγ subunits

Ion selectivity in voltage gated channels depends on the hydration status of the ion. What is the basis of K+ selectivity in voltage gated K+ channels?

A K+ ion hydrated by a single water molecule is the right size to be stabilized at the pore and pass through after shedding its water molecule

Local mRNA translation can control neuronal plasticity. Which of the following are types of neuronal plasticity that are regulated by local translation?

A and B

What are the three types of ionotropic glutamate receptors?

AMPA, NMDA, Kainate

Acetylcholine is synthesized from the precursors _____ and _____, by the enzyme _____.

Acetyl coenzyme A, choline, chat

36. In his classical experiment, what substance did Otto Loewi transfer from one heart to another, and what effect did it have on the recipient heart?

Acetylcholine; heart rate decreased

Kinases regulate ion channels by:

Adding phosphate groups (phosphorylation) to Serine, Threonine or Tyrosine residues

16. After an injury to the peripheral nervous system, it is possible for chronic pain to develop. This type of pain is referred to as neuropathic pain and many current theories of neuropathic attribute causation to glial cells in the spinal cord. How are these glial cells thought to contribute to chronic pain?

All of the above

19. Astrocytes can greatly influence neuronal activity. How?

All of the above

24. Gap junctions serve which of the following purposes in the nervous system:

All of the above

26. The number of vesicles released from the presynaptic terminal is dependent on:

All of the above

35. For a substance to fit the definition of a neurotransmitter it must meet which of the following criteria?

All of the above

Long term depression is viewed largely as

All of the above

The so-called specific PKMζ inhibitor ZIP was used widely in a variety of rat and mouse studies where it was found that

All of the above

Which of the following are examples of extracellular signaling molecules

All of the above

Which of the following have the capacity to activate microglia

All of the above

Which of the following mechanisms can allow for Calcium entry into the postsynaptic terminal to induce a signaling response

All of the above

While there was a great deal of excitement in the neuroscience community around the idea that PKMζ might be a molecular memory "engine" the subsequent finding that _______ suggests that this story is either wrong or incomplete.

All of the above

When PKA binds cAMP molecules this causes a conformational shift in the kinase that

Allows the regulatory subunit to dissociate from catalytic subunit freeing the catalytic subunit to associate with substrates that it then phoshorylates

A defining pathological finding in fragile X mental retardation in humans and in the mouse model is

An excess of long-thin "immature" spines

The BOLD signal in functional MRI is most dependent upon changes in blood flow in the brain that are regulated by which type of cell?

Astrocytes

The rate at which neurons can fire action potentials is most dependent on

B and C

14. Astrocytes release a certain amino acid that then binds to NMDA receptors and is a required co-transmitter with glutamate at this receptor. What is this amino acid called?

D-Serine

Fragile X syndrome is caused by silencing of a single gene whose function is to

Bind RNA and regulate translation

Cocaine increase synaptic dopamine by

Blocking the dopamine transporter

17. Through which two mechanisms do glial cells modulate synapses?

Both A and B

Endocannabinoids have different types of receptors located throughout the body. Which type of receptor is mainly found in immune cells?

CB2

The most common downstream transcription regulatory target of cAMP/PKA signaling is

CREB

Serotonin released onto the Aplysia sensory neuron induces phosphorylation of ________ leading to a long term change in ___________ that promotes synaptic facilitation.

CREB, transcription

LTP requires an early influx of calcium through NMDA receptors that leads to the activation of which of the following kinases that is important for early LTP

CaMKIIα

Golgi's Reticular Theory and Ramon y Cajal's Neuron Doctrine rivalled each other in the way neurons were portrayed in the brain. How were the two theories different?

Cajal's theory is now more widely accepted because of its hypothesis, which we now know is true, that neurons are individual, non-continuous cells that allow for cell to cell communication in the brain through synapses.

Low frequency stimulation induces LTD through

Calcium influx that activates a phosphatase called calcineurin

Increasing the concentration of extracellular K+ from 5mM to 30mM will do what to the neuronal membrane potential:

Cause a depolarization

There are three calcium channel families: Cav1, Cav2, and Cav3. Which one is considered low voltage activated (meaning it is activated by relatively small changes in membrane voltage)?

Cav3 (T-type)

When calcium and calmodulin molecules bind CaMKIIα this causes a conformational shift in the kinase that

Changes the shape of the regulatory domain such that it bends away from the catalytic domain of the single protein allowing the catalytic subunit to associate with substrates

22. There are two major types of neurotransmitters made in the brain: classical transmitters and neuropeptides. Which of the following statements about these types of neurotransmitters are true?

Classical transmitters are made locally at the synapse and are rapidly synthesized by enzymes.

When many ion channels are opened, what happens to conductance and resistance?

Conductance increases; Resistance decreases

20. Gap junction proteins are made up of two protein families with at least 20 genes that fall into the ________ family and 3 genes that fall into the ________ family

Connexin, pannexin

Glial cells are thought to play a role in epilepsy. How would an anti-convulsant therapeutic potentially decrease neuronal excitability in epilepsy through affecting glial cells?

Decrease calcium signaling in astrocytes

The decrease in the response of the postsynaptic membrane that is observed in early LTD is mediated largely by which two factors

Dephosphorylation of AMPA receptors and removal of these receptors from the postsynaptic membrane

Myasthenia Gravis is caused by

Development of autoantibodies that block the ability of acetylcholine to bind to nicotinic receptors at the neuromuscular junction

Parkinson's disease is caused by a loss of ______ neurons from the _________ .

Dopamine, substantia nigra

Pseudo-unipolar neurons have a single axon coming off the cell body that then splits off into two axons and are usually found in:

Dorsal root ganglion

The selectivity filter of voltage gated ion channels is composed of a series of amino acids that are near the entrance to the channel pore. What is the selectivity sequence for voltage-gated calcium channels?

EEEE

Radial Glia cells are considered the stem cells of the brain, arising from neuroepithelial cells. In humans, at which age are there the highest number of radial glial cells?

Embryonic

Regulating intracellular calcium is critical for neurons because too much intracellular calcium can cause excitotoxicity. Which of the following organelles play a key role in buffering calcium in neurons?

Endoplasmic reticulum and mitochondria

Fragile X mutant mice, a model of the human disease, have which of the following specific changes in plasticity

Enhanced LTD

21. During the cycle of neurotransmitter release, the transmitter is released into the synaptic cleft through what process?

Exocytosis

23. Synaptotagmin binds to calcium ions to cause neurotransmitter release. Synaptotagmin has very high affinity (1-10nM) affinity for Ca++. True or false

False

41. TRUE or FALSE. The quantal size is dramatically increased during the induction of long term potentiation and in many other forms of synaptic plasticity indicating that the quantal size in a neuron is always changing.

False

44. TRUE or FALSE. The sodium-potassium ATPase pump has no effect on the resting membrane potential and does not consume energy (i.e. it is electroneutral).

False

TRUE or FALSE. The equilibrium potential of potassium is the membrane voltage at which no potassium ions are physically allowed to cross the membrane?

False

Na+ channels and K+ channels are different in their time course for opening and closing. What is the typical time course for a Na+ ion channel?

Fast and inactivating

What kind of transport is dependent on kinesin motor proteins?

Fast anterograde

Short term plasticity refers mostly to:

Fast changes in neurotransmitter release mediated by residual calcium or depletion of readily releasable pools of synaptic vesicles

NMDA-Rs serve as coincidence detectors because two things must happen simultaneously in order for the channel to get activated. What are these two events?

Glutamate must bind to the receptor and Mg+ must be removed from the pore

Which of the following proteins has intrinsic GTPase activity and sets the duration of signaling after activation of a GPCR

Gα proteins

GPCRs couple directly to

Heterotrimeric G proteins

34. L-Type calcium channels are ______ voltage activated and P/Q-Type calcium channels are _________voltage activated.

High, High

32. During development, the intracellular concentration of Cl- is _____ and the equilibrium potential for Cl- sits _____ the resting membrane potential causing depolarization upon the opening of ligand-gated Cl- channels.

High; above

For some types of ion channels, multiple subunits must come together to form a functional ion channel pore. What is the difference between a hetero-oligomer and a homo-oligomer?

Homo-oligomers are made up of the same type of subunits

The increase in the response of the postsynaptic membrane that is observed in early LTP is mediated largely by which two factors

Increase in phosphorylation of AMPA receptors and increase in their trafficking to the membrane

Late LTP is associated with

Increased gene expression and formation of mushroom shaped spines

How can neurons decrease resistance inside their axons (Ri)?

Increasing axon diameter

Gαi proteins produce which of the following cellular responses

Inhibition of adenylyl cyclase and inhibition of cAMP accumulation

Translation is the process of creating peptides from mRNAs. What is the rate limiting step in translation regulation? This is the step that is most heavily influenced by cellular kinases and is involved in neuronal plasticity.

Initiation

Neurons, sitting at resting membrane potential, normally have a high ____ potassium ion concentration and a high ____ sodium ion concentration.

Intracellular , Extracellular

In voltage-clamp experiments, a downward deflection in current usually indicates

Inward current (e.g. depolarlization)

15. When astrocytes get activated, they increase in size, release inflammatory factors, and show increased calcium levels. What kinds of events can activate astrocytes?

Ischemia or direct mechanical damage

Reversal potential can be reached when permeability for a given ion becomes so high that it dominates the overall permeability of the cell. As sodium's permeability gets higher and higher during an action potential and the membrane voltage becomes more and more positive, what happens to its driving force?

It gets smaller and smaller, eventually hitting its reversal potential

The atypical PKC PKMζ is thought to be a "constitutively" active protein kinase because

It has no regulatory domain

The permeability of ions can vary at different stages of excitability and during the action potential. When a cell is at resting membrane potential, the cell membrane is most permeable to which ion?

K+

The resting membrane potential in neurons is primarily determined by which two ions:

K+ and Na+

42. Which of the three hypotheses about synaptic vesicular exocytosis would you expect to predominate in fast-spiking neurons?

Kiss and run

What magnitudes of tau and lambda might you expect in a synaptic connection that is highly efficacious (e.g. a synapse that has undergone LTP)?

Large tau and large lambda

Which type of axon would have the fastest action potential conduction velocity?

Large, myelinated axons

When blocking specific ion channels, significant changes in current can be observed during the action potential. What can be observed with TTX, the Na+ channel blocker?

Mainly outward currents remained

There are multiple types of opioid ligands that bind to specific types of opioid receptors. What opioid receptor do endorphins and morphine preferentially bind to?

Mu

Certain cation chloride co-transporters are expressed at different levels depending on the developmental stage of the organism. Which cation chloride cotransporter is strongly expressed during early embryonic development of the nervous system in rodents and humans?

NKCC1

The permeability of ions can vary at different stages of excitability and during the action potential. When the cell first reaches action potential threshold, the cell membrane is becoming most permeable to which ion?

Na+

Changes in membrane potential can induce changes in current and ion flow. When sodium's reversal potential is exceeded to the more positive side (e.g. +70 mV), what happens to Na+ flow in the neuron?

Na+ flows out of the cell

NMDA receptors are non-selective cation channels because they allow the following to flow through them:

Na+, Ca++, K+

When acetylcholine is broken down, it is recycled back into the synapse. Which transporter is responsible for this?

Na+/Choline Transporter

Catecholamines are primarily removed from the synaptic cleft by

Reuptake transporters found on the post synaptic membrane

Mutations in ion channels can cause important genetic diseases that are often called channelopathies. Mutations in some ion channels can cause intractable pain. Which sodium channel is mutated in the intractable pain disease called Primary Erythromelalgia?

Nav1.7

There are multiple types of voltage gated sodium channels. What is the voltage gated sodium channel that is primarily expressed in nociceptive neurons in the peripheral nervous system and is resistant to TTX?

Nav1.8

As opposed to early LTP, late LTP is dependent on

New gene expression through increased transcription and local translation

Approximately how excitable are neurons during the peak of an action potential when voltage gated sodium channels are entering the inactivation phase?

Not excitable

43. If you were to administer 10 nM concentration of tetrodotoxin to the voltage-gated sodium channel isoform, Nav1.8, what effect would this have on the channel?

Nothing, Nav1.8 is tetrodotoxin resistant

TRPV1 is a receptor that is largely expressed in nociceptive dorsal root ganglion (DRG) and trigeminal ganglion (TG) neurons and is involved in what type of sensation?

Noxious heat

Myelin in the CNS is made by:

Oligodendrocytes

In what direction would a positively-charged ion flow if ion channels permeable to the ion opened when the resting membrane potential was more positive than the equilibrium potential for that ion?

Out of the cell

How would you describe the current generated from negatively-charged ions flowing into the cell?

Outward current

Pre-pro-peptides are

Peptide neurotransmitter precursors that must be processed before they can be released as active molecules

There is a certain brain area that is largely responsible for the analgesic effects of opioid drugs and the analgesic effects of the endogenous opioid system. What brain area is this?

Periaqueductal gray

A cell's resting membrane potential can be calculated through the Goldman Equation. Goldman's Equation is different than the Nernst Equation because it introduces the concept of what?

Permeability of individual ions

When microglia are activated they enter a state where they release cytokines and take on many properties that are normally associated with macrophages in the periphery during an immune challenge. What is this state called?

Phagocytic state

Gαq G proteins couple to

Phospholipase C

The value of the resting membrane potential is most dependent upon the permeability of which ion species according to the Goldman equation?

Potassium

What would happen to the potassium ion conductance if you added tetrodotoxin (TTX) to your electrophysiological preparation?

Potassium ion conductance would not change

As opposed to LTP at mammalian synapses, long term facilitation at Aplysia synapses is expressed primarily _______ through a __________ mechanism.

Presynaptically, heterosynaptic

31. What are SNARE proteins?

Proteins that promote vesicle fusion to the presynaptic membrane

27. Which family of proteins are in charge of transporting vesicles to active zones and are the energy consuming molecular motors in this process?

Rab GTPases

In the knee jerk response reflex the flexor muscle (hamstring) is inhibited by:

Release of glutamate by the muscle spindle afferent onto a GABAergic interneuron that then inhibits the motor neuron innervating the hamstring.

Which of the following would occur if a neuron had increased sodium ion permeability?

Resting membrane potential would become more positive

29. Using cytoskeleton fibers and kinases, synapsin is an important protein that aids in vesicular localization in synapses. What is its primary function?

Restrict vesicles in place at particular locations

The transcriptome for a given tissue refers to the mRNAs that are expressed in that organ. Which of the following statements are correct?

The brain's transcriptome is distinct compared to other tissues in the human body

If the myelin sheath surrounding the axon of a neuron were to degrade, which of the following would occur?

The length constant would decrease

33. The primary structure of a protein refers to the _____.

The sequence of amino acids that make up the protein

Ion channels, such as voltage gated channels have subunits that have distinct functions. For a voltage gated Ca2+ channel, which of the following subunits is the pore-forming subunit?

The α subunit

Which of the following statements about action potentials are false?

They are usually induced by hyperpolarization

Certain ion channels can have defining characteristics that make them morphologically different than other ion channels but there can also be striking similarities. What similarities do voltage gated Na+ and Ca2+ channels share?

They both are composed of 24 transmembrane domains in a single pore-forming protein

Neuromodulatory neurotransmitters like dopamine acting on D1/D5 receptors and norepinephrine acting on beta adrenergic receptors have which of the following effects on LTP

They can induce LTP by themselves and/or lower the threshold for LTP induction

How do dendrites usually increase their capacity to passively conduct current?

They increase their diameter causing the time and length constant to increase

There is an ongoing debate about how glial cells can modulate the synapse and synaptic transmission. Based on the tripartite synapse theory, how do astrocytes play a primary role in regulation of neurotransmission?

They play an active role in removing and recycling neurotransmitters

The Nerst equation incorporates multiple variables such as ion concentration, temperature, and the charge of ions. What is the main purpose of using the Nerst equation?

To solve for the equilibrium potential / reversal potential of an individual ion

37. TRUE or FALSE. Hyperpolarizing current can be transferred across gap junctions with virtually no synaptic delay.

True

39. TRUE or FALSE. Miniature End Plate Potentials (MEPPs) represent the release of a single quantal packet of neurotransmitters in the absence of synaptic stimulation.

True

TRUE or FALSE. The sodium-potassium ATPase pump is an example of a transmembrane ion channel that requires energy.

True

The length constant (l) has a greater value in axons that are myelinated.

True

The voltage sensor of voltage gated sodium channels is made up of amino acids with positive charge

True

The amino acid precursor for dopamine and norepinephrine is _____ while the amino acid precursor for serotonin is __________ .

Tyrosine, tryptophan

28. There are proteins that allow vesicles to interact with the plasma membrane at the active zone. What kind of protein is synaptobrevin?

V-SNARE

38. Which of the following is correctly ordered?

Voltage-dependent Ca^(2+) channels open; Transmitter release; EPSP; Vesicular endocytosis

Ohm's law is written as Vm - Vequilibrium potential = I*R when considering currents in the nervous system because when Vm = Vequilibrium potential there is ___________ net current flow.

Zero

45. The Kiss and Run hypothesis differs from the classical synaptic vesicle fusion hypothesis in the following way(s)

endocytosis mechanisms that follow vesicle fusion and/or "kissing"

18. When released at the synapse, glutamate:

is removed from the synaptic cleft via EAATs (excitatory amino acid transporters)

There are two types of refractory periods: absolute and relative. What does the absolute refractory period depend on?

nactivation of Na+ channels