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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
Q

How should one think about monoamine NTs?

A

Play a modulatory roles, by increasing or decreasing the gain on glutamatergic or GABAergic neurotransmission

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26
Q

Describe dopamine synthesis. Denote rate-limiting enzyme

A

Tyrosine hydroxylase* converts tyrosine to L-DOPA. DOPA decarboxylase converts L-DOPA to dopamine

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27
Q

Describe noradrenergic synthesis

A

Dopamine is converted into norepinephrine by dopamine β-hydroxylase

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28
Q

Describe adrenergic synthesis

A

Norepinephrine is converted into epinephrine by phenylethanolamine-N-methytransferase

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29
Q

All catecholamines are degraded by…(2)

A

Monoamine oxidases (MAOs) and catechol-O-methyltransferase (COMT)

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30
Q

Catecholamines are concentrated into synaptic vesicles via…What other NT uses this?

A

Vesicular monoamine transporter (VMAT); serotonin

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31
Q

3 major dopaminergic nuclei

A

Substantia nigra, ventral tegmental area (VTA), and the arcuate nucleus of hypothalamus

32
Q

Describe the nigrostriatal dopamine pathway

A

Substantia nigra –> caudate-putamen; modulates motor fxns of the striatum

33
Q

Describe the mesocorticolimbic dopamine pathway

A

VTA –> NA, hippcampus, amygdala, prefrontal; crucial for reward, motivation, emotional memory, executive planning

34
Q

Describe the arcuate nucleus pathway

A

Arcuate nucleus –> anterior pituitary; inhibit prolactin

35
Q

All dopamine receptors are…Give an Gs and Gi example

A

GPCRs; Gs = D1; Gi = D2

36
Q

All antipsychotic drugs are…

A

Antagonists or weak partial agonists at D2

37
Q

All psychostimulant drugs…

A

Promoate dopamine function by inhibiting reuptake/stimulating release

38
Q

2 ways to treat Parkinson’s

A

L-DOPA and D2 agonists

39
Q

What is the most important NE nuclei in the brain? Where does it project? Main function? Lesser functions (2)?

A

Locus ceruleus; all NE innervation to entire forebrain; vigilance/attention; control over ANS and regulating stress/emotional behavior response

40
Q

All NE receptors are…Describe 3 types

A

GPCRs; beta –> Gs; alpha1 –> Gq; alpha2 –> Gi

41
Q

Drugs that block __________ have been used to treat (2)

A

NE transporter; depression and ADHD

42
Q

T/F: Epinephrine acts on the same adrenergic receptors as NE

A

True! (though its mostly used by the adrenal medulla)

43
Q

Describe serotonin synthesis. Denote rate-limiting step

A

The enzyme tryptophan hydroxylase* converts tryptophan to 5-hydroxytryptophan, 5-hydroxytryptophan is converted to 5-hydroxytryptamine (5HT) by aromatic amino acid decarboxylase

44
Q

Most important serotonin nuclei. Projections? Functions?

A

Dorsal raphe nucleus; broad; stress responses, emotional behavior, feeding control, and circadian rhythms

45
Q

4 classes of 5-HT receptors

A

5HT1 –> Gi; 5HT2 –> Gq; 5HT3 –> ligand-gated; 5HT4-7 = Gs

46
Q

Describe the two functions of new antipsychotic drugs

A

In addition to blocking D2 dopamine receptors, also antagonize 5HT2A receptors

47
Q

All major hallucinogens are…

A

Partial agonists at 5HT2C receptors

48
Q

Which serotonin receptor is involved with appetite? How?

A

5HT2c receptors are integrally related to control of appetite: agonists decrease feeding while antagonists increase feeding and result in obesity

49
Q

Anti-migraine drugs are agonists at…

A

5HT1D receptors

50
Q

What brain structure uses melatonin?

A

Pineal gland

51
Q

Describe acetylcholine synthesis and degradation/resorption

A

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
Q

Describe cholinergic projections

A

Brainstem nuclei –> project widely, important for sleep; Medial septal and diagonal band and nucleus basalis of Meynert –> hippocampis; important for cognition

53
Q

Where else do we find cholinergic neurons?

A

Interneurons in striatum

54
Q

Describe acetylcholine’s receptors

A

Ligand-gated: nicotinic, fluxes cations (excitatory); GPCRs: muscarinic, Gi or Gq

55
Q

What does the drug used to treat Parkinson’s disease do?

A

Muscarinic cholinergic antagonist (based on their striatal interneuron function)

56
Q

What does the drug used to treat Alzheimer’s disease do?

A

Acetylcholinesterase inhibitor

57
Q

How does Botulinum toxin work?

A

Blocks ACh release

58
Q

Describe histamine synthesis

A

Histidine –> histamine by histidine decarboxylase

59
Q

What single nucleus synthesizes histamine? Where does it project? Main effect?

A

Tuberomammillary nucleus of the hypothalamus; widespread; sleep/wake cycles

60
Q

Describe three groups of peptides

A
  1. Hypothalamic releasing/inhibitory factors; 2. Feeding and “gut-brain” peptides 3. Tachykinins (regulation of nociception)
61
Q

Describe ways peptide NTs are different than others (4)

A
  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
Q

Describe peptide NT synthesis

A

Prepropeptide gene –> prepropeptide mRNA –> prepropeptide protein –> propeptide (in rough ER) –> peptide –> dense core vesicles

63
Q

T/F: Most peptide NTs are derived from larger proteins

A

True! POMC –> ACTH, beta-endorphin, alpha-MSH

64
Q

T/F: Most peptidergic neurons only use a peptide NT

A

False! Most also use a small NT

65
Q

Describe orexin. Projections (strongest)/function?

A

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
Q

What disorder is associated with orexin?

A

Narcoleps in people who do not have orexin neurons

67
Q

Orexin receptors

A

OX1 and OX2, but GPCRs

68
Q

Three types of opioid peptides and associated functions/receptors

A

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
Q

Opiate drugs target which receptor?

A

Mu

70
Q

Nucleosides are important ___________ NTs. They include (3); where are they used?

A

Modulatory; ATP, adenosine, several di- and tri-nucleosides; released in most synapses w/ other NTs

71
Q

Describe adenosine’s effects and name an important drug

A

Crucial role in regulating alertness and sleep: accumulates during wakefulness to promote sleep; adenosine receptor antagonists = caffeine

72
Q

Name 2 lipid-derived NTs and their precursor

A

Anandamine and 2AG (endocannabinoids); derived from arachidonic acid

73
Q

Describe endocannabindoid synthesis, receptor, and effects

A

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
Q

Describe NO synthesis. Where is it synthesized? What does it act on? Final effects?

A

Derived from arginine by nitric oxide synthase; postsynaptically; presynaptic cGMP production –> modulation of NT release

75
Q

Therefore, like endocannabinoids, NO serves an important _________ function

A

Modulatory

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