ch 6 section 3
___________ is estimated to be the primary neurotransmitter at 50 percent of the excitatory synapses in the CNS.
Glutamate
The IPSP is a ________graded potential that lessens the likelihood that the postsynaptic cell will depolarize to threshold and generate an action potential.
Hyperpolar
NE is found in both the CNS and PNS, while Epi is found mainly in the PNS. The adjective ____________ arises historically from nineteenth-century physiologists who referred to NE and Epi as noradrenaline and adrenaline, respectively
"adrenergic"
_____________is an important neurotransmitter in the CNS and PNS
Norepinephrine
Low doses of botulinum toxin _______ are injected therapeutically to treat a number of conditions, including facial wrinkles, severe sweating, uncontrollable blinking, misalignment of the eyes, and others.
(Botox)
The bacillus Clostridium tetani produces a toxin called ______ ______ which is a protease that destroys SNARE proteins in the presynaptic terminal so that fusion of vesicles with the membrane is prevented, inhibiting neurotransmitter release. Ultimately, this causes excess muscle contraction and a rigid or spastic paralysis
(tetanus toxin)
There are 2 subtypes of ionotropic glutamate receptors:
1. AMPA receptors (identified by their binding to α-amino-3 hydroxy-5 methyl-4 isoxazole proprionic acid), and 2. NMDA receptors (which bind N-methyl-D-aspartate).
neurotransmitters are involved in ___________________,
rapid communication
General factors that determine synaptic strength
1. area of synaptic contact 2. nerotransmitter reuptake 3. enzymatic destruction of neurotransmitter 4. geometry of diffusion pathway
Pre-synaptic factors that determine synaptic strength (4)
1. availability of neurotransmitter 2. amt of precursor molecules 3. axon terminals membrane potential 4. activates receptors on the terminal axon Ca2+
Possible actions of drugs on a synapse (4)
1. increase leakage of neurotransmitters- leads to breakdown of enzymes 2. increase neurotransmitters in cleft- more binding to receptors 3. inhibits, releases and synthesis of neurotransmitter 4. blocks enzymes needed to breakdown neurotransmitters
Postsynaptic factors that determine synaptic strength (3)
1. past history of electrical state 2. neurotransmitters act on postsynaptic neuron 3. Desensitization of receptors
To terminate the signal in a chemical synapse, the unbound neurotransmitters must be removed from the synaptic cleft. This is accomplished by: 1. 2. 3. 4.
1. reuptake- ATP back into the presynaptic neuron 2. Transport into Glial Cells- degrades 3. Diffusion away from receptor 4. Enzymatic transformation in inactive substances
Alzheimer's disease affects 10% to 15% of people over age ___, and 50% of people over age __.
65, 85
Because of the degeneration of cholinergic neurons, this disease is associated with a decreased amount of ___ in certain areas of the brain and even the loss of the postsynaptic neurons that would normally respond to it.
ACh
_______________ is a major neurotransmitter in the PNS at the neuromuscular junction and in the brain.
Acetylcholine (ACh)
________________ protein that breaks down ACh
Actycholinesterase
Many cholinergic neurons in the brain degenerate in people with _________ ________, a brain disease that is usually age related and is the most common cause of declining intellectual function in late life.
Alzheimer's disease
_________ destroys snare proteins that causes reduced muscle contraction and paralysis
Botulism
changes in the brain
Brains show dramatic shrinkage from cell loss and widespread debris This may start 20 years or more before diagnosis Synapses begin to fail due to : Accumulation of beta-amyloid (call beta-amyloid plaques); this occurs OUTSIDE the neurons Interferes with neuron-to-neuron communication at synapses and causes cell death Accumulation of the protein tau (called tau tangles) INSIDE neurons Tau tangles block the transport of nutrients and other essential molecules
The amino acid neurotransmitters are by far the most prevalent neurotransmitters in the _____, and they affect virtually all neurons there.
CNS
_____________-- _______________ are found in widespread locations throughout the CNS and PNS in pathways regulating a wide range of physiological functions including appetite, pain sensation, mood, memory, and locomotor activity.
Cannabinoid receptors
Biogenic amines
Catecholamines Dopamine (DA) Norepinephrine (NE) Epinephrine (Epi) Serotonin (5-hydroxytryptamine, 5-HT) Histamine
__________ __________ low amount of copper, iron and zinc are disrupted in AD; could affect tau, APP, and APOE
Cellular hypothesis
Neurons that release ACh are called __________neurons.
Cholinergic
_________________ __________ AD is caused by reduced synthesis of neurotransmitter acetylcholine
Cholinergic hypothesis
_________ during the action potential opens voltage-gated Ca^(2+) channels in the plasma membrane of the axon terminal, and Ca^(2+) flows into the neuron
Depolarization
Excitatory chemical synapses generate an _________________________________
Depolarizing effect
Examples of neuropeptides include:
Endogenous opioids Beta-endorphin Dynorphins Enkephalins Morphine and codeine are synthetic opioids that are used as analgesics (pain reducers)
____________ another biogenic amine, is not a common neurotransmitter in the CNS, but it is the major hormone secreted by the adrenal medulla.
Epinephrine,
Amino acids
Excitatory amino acids; for example, glutamate Inhibitory amino acids; for example, gamma-aminobutyric acid (GABA) and glycine
Purines
For example, adenosine and ATP
Neuropeptides
For example, endogenous opioids, oxytocin, tachykinins
Gases
For example, nitric oxide, carbon monoxide, hydrogen sulfide
Although it is not one of the 20 amino acids used to build proteins, it is classified with the amino acid neurotransmitters because it is a modified form of glutamate.
GABA
Synapses that use _______ are also among the many targets of the ethanol found in alcoholic beverages.
GABA
_________neurons in the brain are small interneurons that dampen activity within neural circuits. Postsynaptically, GABA may bind to ionotropic or metabotropic receptors.
GABA
Amino acid neurotransmitters at inhibitory synapses include _______and ___________.
GABA and glycine
________ ______ _________ (LSD) stimulates the 5-HT2A subtype of serotonin receptor in the brain, causing intense visual hallucinations.
Lysergic acid diethylamide
Neuroeffector Communication
Many neurons of the PNS synapse not on other neurons but at neuroeffector junctions on muscle, gland, and other cells. The events that occur at neuroeffector junctions are similar to those at synapses between neurons. The neurotransmitter is released from the efferent neuron upon arrival of an action potential, diffuses to the surface of the effector cell, and binds to receptors on that cell's plasma membrane. The receptors on the effector cell may be either ionotropic or metabotropic.
_________ ___________ poor functioning blood brain barrier allows for Herpes simplex virus type 1 and/or chronic bacterial infections
Neurovascular hypothesis
_______ _________damages nerve processing and leads to tau deposits
Myelin breakdown
_____________ also may change the presynaptic cell's synthesis, release, reuptake, or metabolism of a transmitter.
Neuromodulators
_______________ often modify the postsynaptic cell's response to specific neurotransmitters, amplifying or dampening the effectiveness of ongoing synaptic activity.
Neuromodulators
____________ are composed of two or more amino acids linked together by peptide bonds. About 100 neuropeptides have been identified, but their physiological functions are not all known.
Neuropeptides
___________ _________ in the brain are important in cognitive functions and behavior. The presence of nicotinic receptors on presynaptic terminals in reward pathways of the brain explains why tobacco products are among the most highly addictive substances known
Nicotinic receptors
Gases are not released by exocytosis of presynaptic vesicles, nor do they bind to postsynaptic plasma membrane receptors. They are produced by enzymes in axon terminals (in response to Ca^(2+) entry), and simply diffuse from their sites of origin in one cell into the intracellular fluid of other neurons or effector cells, where they bind to and activate proteins. Examples include:
Nitric oxide Carbon monoxide Hydrogen sulfide
Alzheimers disease amygdala
Part of brain that manages emotions During AD, damage to this region causes: Emotional instability Fear Anger Mood swings Paranoia Temper Anxiety
Alzheimers disease brain stem
Progressive damage to brain stem causes changes in: Sleep patterns Trouble swallowing Erratic blood pressure Heart arrhythmia
Calcium ions activate processes that lead to the fusion of docked vesicles with the synaptic terminal membrane, and their interaction with _____ _______
SNARE proteins.
Some chemical weapons, such as the nerve gas ________, inhibit acetylcholinesterase, causing a buildup of ACh in the synaptic cleft
Sarin
_________ is produced from tryptophan, an essential amino acid
Serotonin
_________(5-hydroxytryptamine, or 5-HT) is a neuromodulator involved at virtually every structure in the brain and spinal cord and operates via at least 16 different receptor subtypes
Serotonin
Mechanism of Long-Term Potentiation
Step 1. Presynaptic neuron fires action potentials. Step 2. Glutamate is released from presynaptic terminals. Step 3. Glutamate binds to both AMPA and NMDA receptors on postsynaptic membranes. Step 4. Depolarizing EPSP of the postsynaptic cell mediated via AMPA channels ( influx). Step 5. The depolarization through the AMPA channels allows the magnesium ion blocking the NMDA channels to move and activate the channel. NMDA-receptor channels mediate a substantial influx. Step 6. Calcium enters the cell. Step 7. Calcium ions activate second-messenger systems in the postsynaptic cell that includes persistent activation of multiple protein kinases, stimulation of gene expression and protein synthesis, and an increase in sensitivity of the postsynaptic neuron to glutamate. Step 8. This second-messenger system can also activate long-term enhancement of presynaptic glutamate release via retrograde signals that have not yet been identified
What is Tau Protein?
Tau helps to support neuron cytoskeleton Cytoskeleton has microtubules When phosphorylated, tau stabilizes microtubules In AD, becomes hyperphosphorylated and threads/tangles form
What is Amyloid Beta?
Transmembrane protein Important for neuron growth, survival, and repair In AD, 2 enzymes (gamma secretase and beta secretase) cause APP to be broken into small pieces These small pieces clump and form deposits known as plaques.
Benzodiazepine drugs such as _____________ and _____________ reduce anxiety, guard against seizures, and induce sleep by increasing flux through the GABA receptor.
alprazolam (Xanax) and diazepam (Valium
The biogenic amines are small, charged molecules that are synthesized from ____________.
amino acids
Amino acid neurotransmitters at excitatory synapses include ____________ and ___________.
asparte, glutamate
Toxins of the Clostridium botulinum bacilli, which cause _________, also block neurotransmitter release from synaptic vesicles by destroying SNARE proteins. They target excitatory synapses that activate skeletal muscles; botulism is characterized by reduced muscle contraction, or a flaccid paralysis
botulism
These defects and those in other neurotransmitter systems that are affected in this disease are related to the __________________-.
declining language and cognitive abilities, confusion, and memory loss that characterize individuals with Alzheimer's disease
Approximately 90% of the body's total serotonin is found in the _________ ___________, 8% is in ___________ _______ ____ ______ ________, and only 1% to 2% is found in the _________
digestive system, blood platelets and immune cells, brain
Catecholamines, including _____________, ____________-- and _______________ all contain a catechol ring and an amine group, which is why they are called ____________They are formed from the amino acid tyrosine.
dopamine, norepinephrine, and epinephrine/ catecholamines
The most common biogenic amines are
dopamine, norepinephrine, serotonin, and histamine
______________ stimulates GABA synapses and simultaneously inhibits excitatory glutamate synapses, with the overall effect being global depression of the electrical activity of the brain.
ethanol
Serotonin has an _____effect on pathways that are involved in the control of muscles, and an inhibitory effect on pathways that mediate sensations.
excitatory
The EPSP is a __________graded potential that decreases in magnitude as it spreads away from the synapse by local current. Its only function is to bring the membrane potential of the postsynaptic neuron closer to threshold.
excitatory
Normal function of glycinergic neurons is essential for maintaining a balance of ___________ and __________ activity in spinal cord integrating centers that regulate skeletal muscle contraction.
excitatory and inhibitory
Neurotransmitters are released via _________
exocytosis.
_________ is the major neurotransmitter released from inhibitory interneurons in the spinal cord and brainstem. It binds to ionotropic receptors on postsynaptic cells that allow 〖"Cl" 〗^− to enter.
glycine
_______ is made from the amino acid histidine.
histamine
Inhibitory chemical synapses generate an ____________________________________
hyperpolarizing affect: lessons the chance of depolarizing
neuromodulators tend to be ________________________________such as learning, development, and motivational states.
involved in slower events
Receptors for neurotransmitters influence ____ ________ that directly affect excitation or inhibition of the postsynaptic cell, and these mechanisms operate within milliseconds
ion channels
The ___________ ______________ increases flux into the cell, resulting in hyperpolarization (an IPSP) of the postsynaptic membrane.
ionotropic receptor
All adrenergic receptors are __________________ and thus use second messengers to transfer a signal from the surface of the cell to the cytoplasm
metabotropic
The catecholamine neurotransmitters are broken down in both the extracellular fluid and the axon terminal by enzymes such as __________ ___________
monoamine oxidase (MAO).
ACh binds to __________(G protein-coupled) or __________ (ligand-gated ion channel) receptors.
muscarinic , nicotinic
Receptors for________________ bring about changes in metabolic processes in neurons. Such changes can occur over minutes, hours, or even days and include alterations in enzyme activity or, through influences on DNA transcription, in protein synthesis.
neuromodulators
Adrenergic receptors are utilized by the ________________ __________________ and ____________________
neurotransmitters norepinephrine (NE), epinephrine (Epi)
This results in _________ of postsynaptic ACh receptors initially causing uncontrolled muscle contractions, but ultimately leading to receptor desensitization and paralysis.
overstimulation
Selective serotonin reuptake inhibitors such as ____________ (Paxil) are thought to aid in the treatment of depression by inactivating the presynaptic membrane 5-HT transporter, which mediates the reuptake of serotonin into the presynaptic cell.
paroxetine
In addition to the GABA binding site, this receptor has several additional binding sites for other compounds, including:
steroids, barbiturates, and benzodiazepines.
This becomes apparent in cases of poisoning with the neurotoxin ______, an antagonist of glycine receptors. Victims experience hyperexcitability throughout the nervous system, which leads to convulsions, spastic contraction of skeletal muscles, and ultimately death due to impairment of the muscles of respiration.
strychnine
Axon terminals of the presynaptic neuron hold the ________ _________ that contain neurotransmitter molecules.
synaptic vesicles
________destroys snare proteins that causes excess muscle contraction and paralysis
tetanus
These receptors are the principal target of _____________________________ the principal psychoactive constituent of plants in the Cannabis genus.
tetrahydrocannabinol (THC),