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DBB > Plasticity > Flashcards

Plasticity Flashcards

1
Q

How is glutamate synthesised?

A

from glutamine via glutaminase

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2
Q

What are the types of glutamate vesicles?

A

VGLUT1
VGLUT2
VGLUT3

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3
Q

What are the implications of VGLUT1 and where are they found?

A

knockouts die ~ 3 weeks after birth

cortex and hippocampus

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4
Q

What are the implications of VGLUT2 and where are they found?

A

knockouts die at birth

subcortical structures

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5
Q

What are the implications of VGLUT3 and where are they found?

A

knockouts survive but are deaf

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6
Q

How is glutamate inactivated?

A

by excitatory amino acid transporters 1 and 2
uptake glutamate into astrocytes
glutamate + glutamate synthetase = glutamine

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7
Q

What are the types of glut receptor?

A

ionotropic; AMPA, NMDA, Kainate

metabotropic; mGluR1-8

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8
Q

What are the mechanisms of ionotropic receptors?

A

AMPA; Na+
NMDA; Na+ and Ca2+ (has a sodium block)
kainate; Na+

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9
Q

What are the mechanisms of metabotropic receptors?

A

inhibit cAMP formation

activate second messenger system

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10
Q

What are the major reward pathways and which NT mediates it?

A

VTA - NAcc via dopamine

PFC - VTA via glutamate

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11
Q

What is drug sensitisation?

A

with each dose there is an increased response to the drug; measured by locomotion
7 day withdrawal then re-exposure elicits greatest hyperactive response

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12
Q

How can relapse be modelled in animals?

A

train rats to self-administer drugs using a lever
drug-associated cue; light (e.g. smoke/needle)
after protracted withdrawal re-exposure to the associated cue induces high active lever presses

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13
Q

How can drugs affect dendritic spines?

A

repeated cocaine = increased accumbal spine density, length and branching
spine density only altered when cocaine given in novel environment
spine density altered by drug not instrumental learning

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14
Q

What is the structure and function of spines?

A

spines protrude from dendrites
AMPAR and NMDAR are located on spines
spine head size correlates with number AMPAR
spine density correlates with connectivity

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15
Q

In what circumstances can spines be abnormal?

A

mental disorder patients and drug addicts show abnormal density and morphology

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16
Q

What are the limitations of spine morphology research?

A

could be silent synapses

could be the same amount of connectivity

17
Q

What are the effects of drugs on accumbal dendritic morphology?

A

increased dendritic branching, length and density
SA of drugs not natural rewards
dose-dependent increases that dissipate; role in initial risk of relapse

18
Q

What are the effects of drugs on VTA synaptic potentiation?

A

transient increases in AMPAR + locomotion; EA
potentiated AMPAR following cocaine but not natural reward; SA
only a single exposure is requires
transient implicates role in initiation of sensitisation

19
Q

What are the effects of drugs on NAcc synaptic potentiation?

A

behavioural sensitisation + increased AMPAR; develops as a function of withdrawal
repeated exposures required
insertion of GluR2-lacking AMPAR; pass Ca2+
- Naspm inactive GluR2-lacking AMPAR diminished cocaine-seeking; GluR2-lacking AMPAR responsible for cocaine-seeking
impaired NMDAR-mediated LTD

20
Q

What are the effects of drugs on accumbal neuronal ensembles?

A

increased ensemble activity and context-specific psychomotor sensitisation
specific ensembles are responsible for encoding the association between drug and administration environment; Daun02 inactivation

21
Q

Which addiction-like behaviours can be measured in the rat?

A

motivation; progressive ratio
use despite consequences; footshock
difficulty limiting intake; seeking after drug removed

22
Q

What can addiction-like behaviour experiments in rats tell us?

A

similar number of rats become addicted as humans ~20%
relapse test after period of withdrawal
‘addict-like’ rats show increased SA during long-access session

23
Q

What is context-specific sensitisation?

A

neuronal activity and behavioural response are only sensitised in a specific context

DBB (6 decks)

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