Neurotransmitter Review

Question 1

Molecular structure of Ligand-gated ion channels

Answer 1

4 transmembrane regions of a subunit, 4-5 subunits combine to form a channel.

Question 2

GPCR Structure

Answer 2

Single polypeptide with 7 TM domains

Question 3

Neurotrophic factor reception

Answer 3

Usually dimerized receptors that are TKs.

Question 4

Major excitatory NT

Answer 4

Glu, very ubiquitous and only a minute fraction is packaged into vesicles.

Question 5

Two types of Glu receptors

Answer 5

Ligand Gated Na/Ca channels = AMPA, NMDA, Kainate

GPCR = mGluR 1-8 (Modulatory effects and autoreceptors)

Question 6

How to astrocytes regulate glutamatergic transmission?

Answer 6

They buffer synaptic glutamate levels and protect nearby neurons from excitotoxicity. Astrocytes take up glutamate using GLT-1 (also transport K and Na).

Question 7

Major inhibitory NT

Answer 7

GABA, 40-50% of neurons use.

Question 8

Two major classes of GABA receptors

Answer 8

Ligand gated Cl channels = GABAa

GPCR= GABAb (modulatory effects and autoreceptors).

Question 9

How is GABA synthesized?

Answer 9

It is made from glutamate via glutamic acid decarboxylase, and degraded by GABA transaminase.

Question 10

How do sedative hypnotics (Benzos, barbiturates, alcohol) work?

Answer 10

By promoting the activity of GABAa receptors.

Question 11

How do anticonvulsant drugs (like vigabatrin) work?

Answer 11

By promoting GABA synthesis or preventing its degradation/reuptake.

Question 12

Major inhibitory NT in spinal cord?

Answer 12

Glycine

Question 13

How to induce seizures?

Answer 13

Glycine receptor antagonists, like strychnine.

Question 14

Class of glycine receptors

Answer 14

Strychnine-sensitive glycine receptor (ligand gated Cl- channel)

Question 15

What else is glycine good for?

Answer 15

Co-agonist for NMDA receptor (not responsive to strychnine)

Question 16

Catecholamine degradative enzymes

Answer 16

MAO and COMT

Question 17

Catecholamine synthesis pathway

Answer 17

Tyrosine (TH) L-DOPA (AADC) Dopemine (DBH) NE (PNMT) E

Question 18

Three major dopaminergic pathways in brain

Answer 18

1) Nigrostriatal (movement)
2) Mesocorticolimbic (VTA to NAcc) – motivation/addiction/emotion
3) Tuberoinfundibular (Arcuate nucleus to anterior pituitary) – prevents release of prolactin

Question 19

Dopamine Receptors

Answer 19

All GPCR

D1, D5 – Gs

D2, D3, D4 –Gi, autoreceptors

Question 20

Antipsychotic drug action

Answer 20

D2 antagonists.

Question 21

Psychostimulant (meth, cocaine, ritalin)

Answer 21

Inhibit reuptake or stimulate release of DA.

Question 22

Treatment of PD

Answer 22

L-DOPA or D2 agonists.

Question 23

Noradrenergic projections

Answer 23

Locus ceruleus and other brainstem nuclei to cortex, cerebellum, and tectum.

Question 24

Noradrenergic receptors

Answer 24

All are GPCR

B – GS
a1 – gq
a2– gi (autoreceptor)

Question 25

Antidepressant drug effect on NE

Answer 25

Suppress reuptake

Question 26

Synthesis of serotonin/melatonin

Answer 26

Tryptophan (tryptophan hydroxylase) 5HTP (AADC) 5HT (5HT N-acetylase) 5HT N-acetylase (5hydroxyindole o methyltransferase) melatonin

Question 27

Where is melatonin utilized?

Answer 27

Pineal gland. Function unknown.

Question 28

Serotonergic Projections start from...

Answer 28

Dorsal raphe nucleus (midbrain)

Question 29

5HT receptors

Answer 29

5HT1 -- Gi, autoreceptor 5HT2 -- Gq 5HT3 -- ligand gated 5HT4-7 -- Gs

Question 30

Functions of serotonin

Answer 30

Regulating stress responses and emotional behavior, regulating eating/weight control

Question 31

How do antidepressants affect 5HT

Answer 31

Prevent reuptake

Question 32

New antipsychotic drugs

Answer 32

D2 antagonists, but also block 5HT2a receptors.

Question 33

Hallucinogens

Answer 33

5HT2a partial agonists

Question 34

Antimigrane Drugs (triptans)

Answer 34

5HT1d agonists.

Question 35

Acetylcholine synthesis

Answer 35

Choline + Acetyl CoA (Choline acetyltransferase) Acetylcholine (AChE) Choline + Acetate

Question 36

Most important ACh Projection in brain

Answer 36

Hippocampus

Question 37

Acetylcholine in striatum?

Answer 37

yes in interneurons

Question 38

Acetylcholinergic projections

Answer 38

1) Basal forebrain nuclei (medial septal nucleus, diagonal band, nucleus basalis) project to hippocampus and are important for cognition. 2) Brainstem nuclei (dorsolateral tegmentum in pons) project widely and are important for sleep.

Question 39

Why is smoking addictive?

Answer 39

Nicotine is a strong partial agonist at central nicotinic cholinergic receptors, which activate dopaminergic neurons in the VTA

Question 40

Acetylcholine and PD

Answer 40

mAChR antagonists used to treat PD (work via striatal circuits), also D2 agonists.

Question 41

AChE inhibitors treat?

Answer 41

Treat dementia (via hippocampal circuits)

Question 42

Side effects of ACh antagonists

Answer 42

tachycardia, dry mouth, blurred vision

Question 43

Botox

Answer 43

Blocks ACh release

Question 44

Curare

Answer 44

Blocks NMJs.

Question 45

Histamine Synthesis

Answer 45

From histidine (histidine decarboxylase) histamine

Question 46

Where is histamine used?

Answer 46

Used solely by the tuberomammilary nucleus in hypothalamus.

Question 47

Histamine receptors

Answer 47

All GPCR H1 -- most important in brain H2 -- inhibits stomach acid H3 -- autoreceptor

Question 48

Function of histamine in CNS

Answer 48

Promotes sedation

Question 49

Where does peptide synthesis occur?

Answer 49

Cell body, must be transported. Also enzymatically degraded (irreversible)

Question 50

What type of receptors do peptide NTs use?

Answer 50

GPCRs only

Question 51

Types of peptide NTs

Answer 51

Hypothalamic factors (CRF, TRF, GnRF) Feeding and Gut peptides (NPY, cholesystokinin, VIP) Tachykinins (substance p--nociception)

Question 52

Orexin used where?

Answer 52

Lateral hypothalamus, but widespread projections

Question 53

Orexin receptors

Answer 53

OX1, OX2 (GPCR)

Question 54

Function of Orexin

Answer 54

Wakefulness

Question 55

Narcolepsy

Answer 55

caused by death of orexigenic neurons

Question 56

Three opioid peptides

Answer 56

Enkephalins (preproenkephalin) Endorphins (POMC) Dynorphin (preprodynorphin derived) Mu delta kappa

Question 57

Nucleoside NTs

Answer 57

ATP released with most NTs, converted to adenosine in synaptic space, many different receptors.

Question 58

Adenosine function

Answer 58

Accumulates during wakefulness to promote sleep, sleep reduces adenosine levels

Question 59

Caffeine

Answer 59

Adenosine receptor antagonist.

Question 60

Endocannabinoids

Answer 60

Anandamide and 2-AG

Question 61

Synthesis of endocannabinoids

Answer 61

Synthesized postsynaptically in response to Ca influx, then released into synapse to act on CB1 and CB2 receptors on presynapse.

Question 62

NO as a NT

Answer 62

Synthesized postsynaptically by NO synthase which is activated by Ca, diffuses to presynapse where it activates cyclic GMP to modulate NT release

Question 63

Main function of retrograde messengers

Answer 63

Modulate NT release.