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Brain and Behavior > Lectures 13: NTs > Flashcards

Lectures 13: NTs Flashcards

1
Q

What packs NT into a synaptic vesicle?

A

Vesicular transport protein

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2
Q

Vesicles bind where on the nerve terminal plasma membrane?

A

Active zone

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3
Q

Ca2+ triggers…(in nerve terminal)

A

Fusion

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4
Q

The vesicle is recaptured via endocytosis and protein?

A

Clathrin

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5
Q

Amino acid NTs (3)

A

Glutamate, GABA, Glycine

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6
Q

Monoamines (4)

A

Catecholamines, indoleamines, acetylcholine, histamine

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7
Q

Catecholamines (3)

A

Dopamine, NE, epi

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8
Q

Indoleamines (2)

A

Serotonin, melatonin

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9
Q

Other NTs (5 classes)

A

Nucleosides (adenosine), lipid-derived (anandamine), gases (NO), neurotrophic factors (BDNF), hormones w/ nuclear receptors (steroids)

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10
Q

Ligand-gated channels create a robust…How many transmembrane regions? How many subunits?

A

Postsynaptic current; 4; 4-5

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11
Q

GPCR has how many transmembrane regions?

A

7

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12
Q

Two other motifs of neurotransmission in the brain

A

Protein tyrosine kinases (neurotrophic factors) and nuclear hormone receptors (steroid hormones)

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13
Q

Glutamate acts through…Examples of each and major role.

A

Ligand-gated channels (rapid neurotransmission, AMPA, NMDA, kainate) and GPCRs (modulatory influences/autoreceptors, mGluR1-8)

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14
Q

What accounts for the vast majority of the brain’s rapid, point-to-point communication?

A

Glutamate acting on ligand-gated channels

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15
Q

Autoreceptors are…

A

Gi

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16
Q

Glutamate can be made from which two pathways? And which enzymes? What enzyme turns glutamate into glutamine? What cell expresses this?

A

Aspartate and alpha-ketoglutarate (transaminase); glutamine (glutaminase); glutamine synthetase; astrocytes

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17
Q

Two glutamate-relevant drugs and their action

A

Ketamine and phencyclidine; NMDA receptor antagonists

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18
Q

GABA acts through…Examples of each. What ion does the first channel flux? What is the second receptor?

A

Ligand-gated channels (GABAa) and GPCRs (GABAb); Cl-; autoreceptor

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19
Q

Describe GABA’s synthesis and degradation

A

GABA is synthesized from glutamate via the enzyme, glutamatic acid decarboxylase (GAD) and degraded by GABA transaminase

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20
Q

How is GABA removed from the synapse?

A

Returned to the nerve terminal via a plasma membrane GABA transporter

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21
Q

How do anticonvulsant drugs work?

A

Either increase GABA synthesis or block reuptake

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22
Q

How do sedative-hypnotic drugs work? What are their effects? Two examples?

A

Promote GABAa receptor function; anticonvulsant/anti-anxiety/pro-sleep; benzos and barbiturates

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23
Q

Where does Glycine primarily serve as a NT? Excitatory or inhibitory? What kind of receptor? Name?

A

Spinal cord; inhibitory; a ligand-gated Cl- channel; strychnine-sensitive glycine receptor

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24
Q

What is a second function of glycine?

A

Glycine can bind with relatively low affinity to NMDA glutamate receptors and thereby enhances the ability of glutamate to activate these receptors

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25
How should one think about monoamine NTs?
Play a modulatory roles, by increasing or decreasing the gain on glutamatergic or GABAergic neurotransmission
26
Describe dopamine synthesis. Denote rate-limiting enzyme
Tyrosine hydroxylase* converts tyrosine to L-DOPA. DOPA decarboxylase converts L-DOPA to dopamine
27
Describe noradrenergic synthesis
Dopamine is converted into norepinephrine by dopamine β-hydroxylase
28
Describe adrenergic synthesis
Norepinephrine is converted into epinephrine by phenylethanolamine-N-methytransferase
29
All catecholamines are degraded by...(2)
Monoamine oxidases (MAOs) and catechol-O-methyltransferase (COMT)
30
Catecholamines are concentrated into synaptic vesicles via...What other NT uses this?
Vesicular monoamine transporter (VMAT); serotonin
31
3 major dopaminergic nuclei
Substantia nigra, ventral tegmental area (VTA), and the arcuate nucleus of hypothalamus
32
Describe the nigrostriatal dopamine pathway
Substantia nigra --> caudate-putamen; modulates motor fxns of the striatum
33
Describe the mesocorticolimbic dopamine pathway
VTA --> NA, hippcampus, amygdala, prefrontal; crucial for reward, motivation, emotional memory, executive planning
34
Describe the arcuate nucleus pathway
Arcuate nucleus --> anterior pituitary; inhibit prolactin
35
All dopamine receptors are...Give an Gs and Gi example
GPCRs; Gs = D1; Gi = D2
36
All antipsychotic drugs are...
Antagonists or weak partial agonists at D2
37
All psychostimulant drugs...
Promoate dopamine function by inhibiting reuptake/stimulating release
38
2 ways to treat Parkinson's
L-DOPA and D2 agonists
39
What is the most important NE nuclei in the brain? Where does it project? Main function? Lesser functions (2)?
Locus ceruleus; all NE innervation to entire forebrain; vigilance/attention; control over ANS and regulating stress/emotional behavior response
40
All NE receptors are...Describe 3 types
GPCRs; beta --> Gs; alpha1 --> Gq; alpha2 --> Gi
41
Drugs that block __________ have been used to treat (2)
NE transporter; depression and ADHD
42
T/F: Epinephrine acts on the same adrenergic receptors as NE
True! (though its mostly used by the adrenal medulla)
43
Describe serotonin synthesis. Denote rate-limiting step
The enzyme tryptophan hydroxylase* converts tryptophan to 5-hydroxytryptophan, 5-hydroxytryptophan is converted to 5-hydroxytryptamine (5HT) by aromatic amino acid decarboxylase
44
Most important serotonin nuclei. Projections? Functions?
Dorsal raphe nucleus; broad; stress responses, emotional behavior, feeding control, and circadian rhythms
45
4 classes of 5-HT receptors
5HT1 --> Gi; 5HT2 --> Gq; 5HT3 --> ligand-gated; 5HT4-7 = Gs
46
Describe the two functions of new antipsychotic drugs
In addition to blocking D2 dopamine receptors, also antagonize 5HT2A receptors
47
All major hallucinogens are...
Partial agonists at 5HT2C receptors
48
Which serotonin receptor is involved with appetite? How?
5HT2c receptors are integrally related to control of appetite: agonists decrease feeding while antagonists increase feeding and result in obesity
49
Anti-migraine drugs are agonists at...
5HT1D receptors
50
What brain structure uses melatonin?
Pineal gland
51
Describe acetylcholine synthesis and degradation/resorption
Synthesized from choline and acetyl-CoA in a single enzymatic step catalyzed by choline acetyltransferase; degraded by acetylcholinesterase in the synapse and choline is taken up
52
Describe cholinergic projections
Brainstem nuclei --> project widely, important for sleep; Medial septal and diagonal band and nucleus basalis of Meynert --> hippocampis; important for cognition
53
Where else do we find cholinergic neurons?
Interneurons in striatum
54
Describe acetylcholine's receptors
Ligand-gated: nicotinic, fluxes cations (excitatory); GPCRs: muscarinic, Gi or Gq
55
What does the drug used to treat Parkinson's disease do?
Muscarinic cholinergic antagonist (based on their striatal interneuron function)
56
What does the drug used to treat Alzheimer's disease do?
Acetylcholinesterase inhibitor
57
How does Botulinum toxin work?
Blocks ACh release
58
Describe histamine synthesis
Histidine --> histamine by histidine decarboxylase
59
What single nucleus synthesizes histamine? Where does it project? Main effect?
Tuberomammillary nucleus of the hypothalamus; widespread; sleep/wake cycles
60
Describe three groups of peptides
1. Hypothalamic releasing/inhibitory factors; 2. Feeding and "gut-brain" peptides 3. Tachykinins (regulation of nociception)
61
Describe ways peptide NTs are different than others (4)
1. Synthesized via standard protein processes in somas (not nerve terminals); 2. Peptide NTs are packaged into large dense core vesicles (exocytosed) not small clear synaptic vesicles; 3. Peptides degraded enzymatically in synapse, no reuptake occurs; 4. Solely act on GPCRs
62
Describe peptide NT synthesis
Prepropeptide gene --> prepropeptide mRNA --> prepropeptide protein --> propeptide (in rough ER) --> peptide --> dense core vesicles
63
T/F: Most peptide NTs are derived from larger proteins
True! POMC --> ACTH, beta-endorphin, alpha-MSH
64
T/F: Most peptidergic neurons only use a peptide NT
False! Most also use a small NT
65
Describe orexin. Projections (strongest)/function?
Name refers to two related peptides used as a neurotransmitter by a small number of neurons in the lateral hypothalamus; wide projections w/ strongest to the histaminergic tuberomammillary nucleus; promotes alertness
66
What disorder is associated with orexin?
Narcoleps in people who do not have orexin neurons
67
Orexin receptors
OX1 and OX2, but GPCRs
68
Three types of opioid peptides and associated functions/receptors
Enkephalins, endorphins, dynorphins; enkephalins and endorphins (mu and delta receptors) promote reward, positive mood, analgesia, and sedation. Dynorphins (kappa receptors) promote analgesia and sedation, but induce negative mood state.
69
Opiate drugs target which receptor?
Mu
70
Nucleosides are important ___________ NTs. They include (3); where are they used?
Modulatory; ATP, adenosine, several di- and tri-nucleosides; released in most synapses w/ other NTs
71
Describe adenosine's effects and name an important drug
Crucial role in regulating alertness and sleep: accumulates during wakefulness to promote sleep; adenosine receptor antagonists = caffeine
72
Name 2 lipid-derived NTs and their precursor
Anandamine and 2AG (endocannabinoids); derived from arachidonic acid
73
Describe endocannabindoid synthesis, receptor, and effects
Synthesized postsynaptically in response to Ca2+ influx, released into the synapse where they act on CB1 receptors located on nearby nerve terminals to regulate NT release; effects = perception, appetite, nociception, reward, and level of consciousness
74
Describe NO synthesis. Where is it synthesized? What does it act on? Final effects?
Derived from arginine by nitric oxide synthase; postsynaptically; presynaptic cGMP production --> modulation of NT release
75
Therefore, like endocannabinoids, NO serves an important _________ function
Modulatory

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