Neurotransmitter Systems

Question 1

Everytime you here raphe what should you think of?

Answer 1

serotonin

Question 2

Where are neurons that make Ach?

Answer 2

in midbrain and pons

stratum of basal ganglia (motor control):

caudate and putamen

Question 3

What does Ach function in?

Answer 3

from striatum: voluntary mvt

from midbrain and pons: baseline excitation to cortex, REM sleep

Question 4

How is Ach synthesized?

Answer 4

from choline and acetate

moved into vesicles via VAchT

removed from synapse thru Achesterase bound to post-syn membrane

Question 5

What are the subtypes of muscarinic receptors in CNS and their type of GPCR?

Answer 5

M1: neuronal; Gq

M4: presynaptic autoreceptor, striatum of basal ganglia; Gi

M5: cerebrovasculature, dopaminergic neurons of basal ganglia; Gq

Question 6

Where are nicotinic cholinergergic receptors located?

What should you know about the subunits?

Answer 6

NMJ

5 subunits coded by 16 diff genes

changing subunits changes properties of channel; in some central synapses allows more calcium in

Question 7

What are the 2 major inhibitory AAs?

Answer 7

GABA

glycine

Question 8

Where do you find GABA?

Answer 8

throughout CNS

spinal cord has least amt

Question 9

What is GABA critical in?

Answer 9

consciousness

motor control

vision

Question 10

How is GABA synthesized?

Answer 10

from glutamate

gutamate decarboxylase (GAD) RL enzyme

transported into vesicles by VGAT

Question 11

What removes GABA from synapse?

Answer 11

GAT

GAT1: on presynaptic terminal –> repackages into vesicles

GAT2: on glial cells surrounding synapse –> converted to glutamine and released to ECF –> taken up by presyn cell and recycled into GABA

Question 12

What type of receptors are gaba-A receptors?

Answer 12

ionotropic: Cl- conductance

activate ipsp in adult neurons

multiple binding sites for benzos, ethanol, steroids –> all potentiate

Question 13

Why do we believe there are a lot of extra-synaptic GABA-A receptors?

Answer 13

site of action for general anesthetics

Question 14

What type of receptors are GABA-B?

Answer 14

metobotropic

Gi/Go –> inhibit Ca channel

presynaptic: regulate NT release
postsynaptic: inhibit post-syn cell

Question 15

Where is glycine found?

Answer 15

spinal cord: major

medulla

much less in higher areas of CNS

Question 16

What does glycine do in general?

Answer 16

mediates many spinal inhibitions

Question 17

What removes glycine from synapses?

Answer 17

GAT proteins (same as GABA)

recycled

Question 18

What characterizes the glycine receptor?

Answer 18

ionotropic (chloride)

influx of chloride –> ipsp

etoh and gen anesthetics bind to it and potentiate it

sychnine binds to it and blocks it

Question 19

What are the purines used as NTs?

How are they stored?

Answer 19

ATP, ADP, adenosine

stored in vesicles: VNUT protein

Question 20

Where are purines found?

Answer 20

virtually everywhere in CNS

special mention to: cortex, cerebellum hippocampus, basal ganglia

Question 21

What are the 2 major classes of purine receptors?

Answer 21

P1 (A receptor): adenosine

P2: x and y

Question 22

What does the P1 receptor bind and where is it?

Answer 22

adenosine

post-syn: sleep induction, general inhibition of neural fxn

presyn: inhibition of NT release

Question 23

What are the P2 receptors and what do they do?

Answer 23

P2X: ionotropic, bind ATP, many subtypes

P2Y: metabotropic, bind ATP, ADP, UTP, UDP, Gi

Fxns: learning and memory (co-relase w/ EAA), modification of locomotor paths

Question 24

What are peptide transmitters?

Answer 24

peptides made in the soma and transported down axon via fast transport

several types: kinins, opioids = most impt

Question 25

What are the 4 types of opiods to know?

Answer 25

endorphins (endogenous morphines) enkephalins dynorphins nociceptin

Question 26

Where are the opiods found?

Answer 26

basal ganglia hypothalamus multiple pontine and medullary sites

Question 27

What is the general fxn of opioids?

Answer 27

modification of nociceptive inputs (cutaneous senses) mood/affect

Question 28

What are the 4 precursors of opioids?

Answer 28

PCOM --\> beta endorphins Pro-encephalin pro-dynorphin orphanin FQ

Question 29

How are opioids removed from the cleft?

Answer 29

probable reuptake enzymatic destruction via enkephalinase, aminopeptidiase

Question 30

What are the 3 types of opiod receptors?

Answer 30

mu: metabotropic kappa, and delta: serpentine

Question 31

What does activation of the mu opiod receptor cause?

Answer 31

analgesia respiratory depression euphoria constipation sedation

Question 32

What does activation of the kappa opiod receptor cause?

Answer 32

analgesia dysphoria diuresis miosis

Question 33

What does activation of the delta opiod receptor cause?

Answer 33

analgesia

Question 34

What do all opiod receptors connect to and what are their cellular effects?

Answer 34

all connect to Gi Mu: K eflux --\> hyperpolarization delta and kappa: decrease calcium influx

Question 35

What are the identified endogenous cannabinoids?

Answer 35

anandamide 2AG (derivatives of arachadonic acid)

Question 36

Where are endocannabinoids found?

Answer 36

broadly distributed in CNS basal ganglia: mood, motor performance spinal cord: modulation of nociception cortex: neuroprotection hippocampus: inh memory formation hypothalamus: hunger

Question 37

What do you need to know about arachidonic acid synthesis?

Answer 37

derived from membrane lipids = arachidonic acid occurs in presynaptic terminal

Question 38

What are the 2 endocannabinoid receptors?

Answer 38

CB1: pre-syn CB2: immune sys, microglia

Question 39

What does the CB1 receptor do?

Answer 39

binds endocannabinoids on presyn cells of EAA and GABA releasing synapses reduces EAA and GABA release Gi anandamide and 2-Ag are equally effective

Question 40

What does the CB2 receptor do?

Answer 40

binds endocannabinoids immune sys fxn: microglia, gut, immune sys in general anti-inflammatory in brain: CB2 activation increases beta amyloid removal