Lectures 13: NTs Flashcards Preview

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Flashcards in Lectures 13: NTs Deck (75):
1

What packs NT into a synaptic vesicle?

Vesicular transport protein

2

Vesicles bind where on the nerve terminal plasma membrane?

Active zone

3

Ca2+ triggers...(in nerve terminal)

Fusion

4

The vesicle is recaptured via endocytosis and protein?

Clathrin

5

Amino acid NTs (3)

Glutamate, GABA, Glycine

6

Monoamines (4)

Catecholamines, indoleamines, acetylcholine, histamine

7

Catecholamines (3)

Dopamine, NE, epi

8

Indoleamines (2)

Serotonin, melatonin

9

Other NTs (5 classes)

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

10

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

Postsynaptic current; 4; 4-5

11

GPCR has how many transmembrane regions?

7

12

Two other motifs of neurotransmission in the brain

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

13

Glutamate acts through...Examples of each and major role.

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

14

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

Glutamate acting on ligand-gated channels

15

Autoreceptors are...

Gi

16

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

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

17

Two glutamate-relevant drugs and their action

Ketamine and phencyclidine; NMDA receptor antagonists

18

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

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

19

Describe GABA's synthesis and degradation

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

20

How is GABA removed from the synapse?

Returned to the nerve terminal via a plasma membrane GABA transporter

21

How do anticonvulsant drugs work?

Either increase GABA synthesis or block reuptake

22

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

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

23

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

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

24

What is a second function of glycine?

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

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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