NTs in the CNS

Question 1

Describe the role of glial cells and their quantity compared to neurons

Answer 1

communication, receptor expression, electrical coupling = support neural function, outnumber neurons 10:1

Question 2

What is the purpose of the blood brain barrier?

Answer 2

stops brain being exposed to unwanted elements from body eg infection

Question 3

List the structures that make up a neurovascular unit.

Answer 3

astrocyte, pericyte, endothelial cell, basement membrane

Question 4

List the major NTs in the brain and separate into excitatory, inhibitory or both

Answer 4

EX: ACh, dopamine, glutamate
INHIB: serotonin, GABA, glycine
BOTH: noradrenaline

Question 5

Describe the cycle of glutamate and glutamine in the CNS

Answer 5

released Glu captured partly by neurons and partly astrocytes which convert most of it to Gln
Gln transported out of astrocyte and taken up by neurons which use it to make Glu

Question 6

What structure allows Glu to enter astrocytes and neurons?

Answer 6

Excitatory amine acid transporter (EAAT)

Question 7

List the 4 types of Glu receptors and differentiate between ionotropic and metabotropic

Answer 7

Ionotropic: NMDA-R, Kainate, AMPA-R Metabotropic: GPCR

Question 8

Briefly describe the NMDA-R

Answer 8

takes milliseconds, Allows specificity, involved in learning and memory, allows movement of charge through central pore (sodium and calcium, blocked by mag), excitatory +ve charge, ionotropic, contains positive allosteric modulation site (glycine favours)

Question 9

Briefly describe Kainate

Answer 9

glu R, takes milliseconds, allows movement of charge through central pore, excitatory +ve charge, ionotropic

Question 10

Briefly describe AMPA-R

Answer 10

takes milliseconds, allows movement of charge through central pore, excitatory +ve charge, ionotropic

Question 11

Briefly describe GPCR

Answer 11

takes seconds, no pore down centre channel

Question 12

Which drugs affect glu receptors?

Answer 12

PCP, memantine and ketamine

Question 13

What happens if you block Glu receptors and why?

Answer 13

since these receptors are excitatory when activated, blocking them can cause inhibition

Question 14

What is the mechanism of action of drugs that affect Glu receptors?

Answer 14

non-competitive antagonist blocking ion movement within pore, doesn’t block Glu, blocks pore

Question 15

What type of block happens in NMDA-R

Answer 15

magnesium block preventing flow of ions

Question 16

Briefly describe GABAA receptor

Answer 16

allows movement of negative charge through central pore (chlorine)=less likely to fire action potential=inhibitory, diversity of subtypes, positive allosteric binding site activation -> inhibitory effect

Question 17

Compare and contrast GABAA receptors with NMDA-R, NTs and modulations

Answer 17

what are they conducting: NMDA-R conduct positive charge, GABAA receptors conduct negative charge
what activates them: NMDA-R activated by glutamate, GABAA receptors activated by GABA
effect on cells: NMDA-R are excitatory and increase likelihood of action potential occurring, GABAA receptors are inhibitory and decrease likelihood of action potential occurring
how is behaviour affected: NMDA receptors behaviour affected by sodium and calcium, GABAA receptor behaviour affected by chloride
modulations: both contain positive allosteric modulations

Question 18

What drugs affect GABAA receptors and what affect do they have?

Answer 18

GABA, benzodiazepines, alcohol, general anaesthetics, barbiturates. these drugs increase the inhibitory affect

Question 19

List the subunits in the GABAA receptor and what affect do different combinations have

Answer 19

2 alpha, 2 beta and a gamma, different combinations result in different affinities for GABA

Question 20

Why does binding of alcohol not stop GABA binding also?

Answer 20

They bind at different sites so alcohol enhances GABA effect when released

Question 21

Describe GABAB receptors

Answer 21

GPCRs, activation stabilizes potassium movement and reduces inward calcium movement, inhibitory

Question 22

What disorder can GABAB receptors help with?

Answer 22

spasticity

Question 23

describe GHB

Answer 23

Date rape drug, agonist (activator) of GABAB receptors = sedative, euphoric effects, unconsciousness and possibly death

Question 24

describe Glycine

Answer 24

NT, positive allosteric modulator for NMDA-R, can be enzymatically made from Glu, packaged into vesicles, inhibitory

Question 25

Which toxins block glycine receptors, what is their effect and why?

Answer 25

strychnine and tetanus toxin block glycine receptors causing over excitation leading to seizures and muscle spasms

Question 26

List monoamine NTs

Answer 26

noradrenaline, serotonin and dopamine

Question 27

Describe monoamine pathways

Answer 27

small numbers of cell bodies arising in upper brainstem, radiate to most cortical areas and present discrete tracts within brain

Question 28

Describe noradrenergic receptors

Answer 28

alpha and beta subtypes, all are GPCRs in their actions, serve variety of roles depending on location eg alpha receptors on neurons and glial cells have motor control, fear and recognition

Question 29

describe serotonin receptors

Answer 29

largest family of receptors with 7 families and at least 14 subtypes, complex, most GPCRs but come 5HT3 which are ionotropic and associated with sleep, appetite, receptors play role in depression

Question 30

describe dopamine tracts

Answer 30

4 main tracts: nigrostriatal which controls motor function and movement, mesolimbic linked to drug dependence, psychoses, delusions
mesocortical mediates cognitive symptoms and affects aspects of schizophrenia
tuberoinfundibular control prolactin secretion

Question 31

list the types of dopamine receptors

Answer 31

D1 like and D2 like

Question 32

Why is Glu referred to as “common currency” for amino acid NTs?

Answer 32

Because Glu can be used as template for other NTs in CNS if necessary enzymes are present eg Glu can be made into GABA, glycine, glutamine etc