Week 5 part 1

Question 1

What does Immunocytochemistry reveal

Answer 1

CB1 is located in axons and axons terminals, indicative of a pre-synaptic site of action

Question 2

What does CB (1)-type cannabinoid receptor mediate?

Answer 2

Physiologic effects of delta (9) - tetrahydrocannabinol, the psychoactive ingredient of the drug marijuana

Question 3

What does antibody shown in hippocampus reveal?

Answer 3

Unusual distribution

Question 4

What is the labelling for CB1?

Answer 4

axonal terminal boutons

Question 5

What is present all around pyramidal cells (CA1)?

Answer 5

Cells with axonal terminal

Question 6

What is present around cell body?

Answer 6

Inhibitory interneurons

Question 7

What does cannabinoids cause?

Answer 7

CB1-dependent inhibition of neurotransmitter release from axon terminals

Question 8

What does the presynaptic localization of CB receptors suggest?

Answer 8

A role for cannabinoids in modulating the release of neurotransmitters from axon terminals

Question 9

Where did THC inhibit acetylcholine release from?

Answer 9

electrically stimulated guinea pig ileum

Question 10

What are the brain regions most often studied?

Answer 10

1. Cerebellum
2. Hippocampus
3. Neocortex

Question 11

What does cannabinoids work as?

Answer 11

Retrograde transmitter

Question 12

What is retrograde signalling

Answer 12

function of one part of a cell is controlled by feedback from another part of the cell, or where one cell sends reciprocal messages back to another cell that regulates it

Question 13

What is an example of retrograde transmitter

Answer 13

Inhibition of voltage-gated calcium channel from axonal terminals mediated by a G protein complex

Question 14

Where is cannabinoid made by?

Answer 14

Dendritic portion

Question 15

What is an example of retrograde signalling

Answer 15

1. AP goes down axon
2. Releases NT like glutamate
3. Acts on the dendrite
4. Retrogradely cannabinoid go back to axonal terminal and will modulate further release from that axon

Question 16

What does cannabinoid intracellularly in the axonal terminal activate?

Answer 16

G protein (GI-A subunit)

decrease CAMP

act directly on cl- channels to block cl- so cl doesnt enter presynaptic terminal

Question 17

What does CAMP increase permeability to?

Answer 17

K+

Question 18

What does inhibition of adenylyl cyclase activity lead to?

Answer 18

Reduction in PKA-mediated phosphorylation of presynaptic potassium channels

Question 19

What does reduction in PKA-mediated phosphorylation of presynaptic potassium channel result in?

Answer 19

Enhancement of potassium channel activity

Question 20

where is CB1 expressed by many regions of the brain?

Answer 20

1. GABAergic interneurons

Question 21

What does cannabinoid cause inhibition of

Answer 21

GABA release by these neurons

Question 22

What does distribution in GABAergic interneuron show?

Answer 22

Have more CB1 receptor than the glutamatergic receptor

Question 23

Where is CB1 found?

Answer 23

Both excitatory and inhibitory terminals

Question 24

What happens in the inhibitory terminals ?

Answer 24

They decrease GABA release

Question 25

Where is CB1 expressed by in some brain regions?

Answer 25

1. Glutamatergic neurons

Question 26

What is an example of glutamatergic neuron?

Answer 26

1. Cerebellar granule cells

Question 27

What does cannabinoid inhibit the release of?

Answer 27

Glutamate

Question 28

What does the overall effect of cannabinoids on the brain represent?

Answer 28

the net outcome of their effect on different types of neurotransmission in different regions of the brain

Question 29

What is creloxp deletion technique?

Answer 29

• Method by which genes can be mopped up in sub population of cells

Question 30

What does generation of conditional CB1 knockout mice allow for?

Answer 30

1. Alteration and deletion of DNA | 2. Regulation of location and timing of gene recombination

Question 31

What is Cre-Recombinase?

Answer 31

1. Site-specific enzyme, catalyses recombination between 2 loxP sites 2. Lox-P site: 34 base pair DNA sequence 3. Location and orientation determines recombination results in deletion

Question 32

What does Cre-Recombinase allow for?

Answer 32

the specific manipulation of DNA based on the direction and location of the two loxPs

Question 33

What does Cre catalyse?

Answer 33

deletion of the DNA between the two loxPs when the two loxPs are in the same direction on one DNA molecule

Question 34

What happens if you knock out CB1 glutamatergic neurons?

Answer 34

abolishes the effect of tHC in terms of affecting analgesia whereas knocking out the CB1 receptor in GABAergic neurons doesn’t

Question 35

What are the effects of THC mediated by?

Answer 35

CB1 receptors in the brain

Question 36

What does CB1 receptors mediate when activated by cannabinoids?

Answer 36

1. presynaptic inhibition of the release of excitatory (glutamate) and inhibitory (GABA) neurotransmitters

Question 37

What does the analysis of CB1-conditional KO mice indicate?

Answer 37

Physiological and behavioural effects of THC are not mediated by CB1 expressing GABAergic neurons