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MTB x > Week 5 part 1 > Flashcards

Week 5 part 1 Flashcards

1
Q

What does Immunocytochemistry reveal

A

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

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2
Q

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

A

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

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3
Q

What does antibody shown in hippocampus reveal?

A

Unusual distribution

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4
Q

What is the labelling for CB1?

A

axonal terminal boutons

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5
Q

What is present all around pyramidal cells (CA1)?

A

Cells with axonal terminal

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6
Q

What is present around cell body?

A

Inhibitory interneurons

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7
Q

What does cannabinoids cause?

A

CB1-dependent inhibition of neurotransmitter release from axon terminals

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8
Q

What does the presynaptic localization of CB receptors suggest?

A

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

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9
Q

Where did THC inhibit acetylcholine release from?

A

electrically stimulated guinea pig ileum

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10
Q

What are the brain regions most often studied?

A
  1. Cerebellum
  2. Hippocampus
  3. Neocortex
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11
Q

What does cannabinoids work as?

A

Retrograde transmitter

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12
Q

What is retrograde signalling

A

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

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13
Q

What is an example of retrograde transmitter

A

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

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14
Q

Where is cannabinoid made by?

A

Dendritic portion

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15
Q

What is an example of retrograde signalling

A
  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
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16
Q

What does cannabinoid intracellularly in the axonal terminal activate?

A

G protein (GI-A subunit)

decrease CAMP

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

17
Q

What does CAMP increase permeability to?

18
Q

What does inhibition of adenylyl cyclase activity lead to?

A

Reduction in PKA-mediated phosphorylation of presynaptic potassium channels

19
Q

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

A

Enhancement of potassium channel activity

20
Q

where is CB1 expressed by many regions of the brain?

A
  1. GABAergic interneurons
21
Q

What does cannabinoid cause inhibition of

A

GABA release by these neurons

22
Q

What does distribution in GABAergic interneuron show?

A

Have more CB1 receptor than the glutamatergic receptor

23
Q

Where is CB1 found?

A

Both excitatory and inhibitory terminals

24
Q

What happens in the inhibitory terminals ?

A

They decrease GABA release

25
Q

Where is CB1 expressed by in some brain regions?

A
  1. Glutamatergic neurons
26
Q

What is an example of glutamatergic neuron?

A
  1. Cerebellar granule cells
27
Q

What does cannabinoid inhibit the release of?

28
Q

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

A

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

29
Q

What is creloxp deletion technique?

A

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

30
Q

What does generation of conditional CB1 knockout mice allow for?

A
  1. Alteration and deletion of DNA

2. Regulation of location and timing of gene recombination

31
Q

What is Cre-Recombinase?

A
  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
32
Q

What does Cre-Recombinase allow for?

A

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

33
Q

What does Cre catalyse?

A

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

34
Q

What happens if you knock out CB1 glutamatergic neurons?

A

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

35
Q

What are the effects of THC mediated by?

A

CB1 receptors in the brain

36
Q

What does CB1 receptors mediate when activated by cannabinoids?

A
  1. presynaptic inhibition of the release of excitatory (glutamate) and inhibitory (GABA) neurotransmitters
37
Q

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

A

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

MTB x (15 decks)

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