lecture 21 LOs

Question 1

what receptors in the PFC mediate working memory

Answer 1

PFC D1 but not D2

Question 2

how can manipulating PFC DA D1 activity change baseline levels of performance

Answer 2

poor performance: extra D1 stimulation will improve functioning
good performance: D1 receptors antagonist impairs functioning

Question 3

which receptors mediate congnitive flexibility

Answer 3

D1 and D2 receptors

Question 4

what does supranormal stimulation of D1 or D2 do to cognitive flexibility

Answer 4

does not affect it

Question 5

what does D4 receptor stimulation impair

Answer 5

set shifting
S shaped function

Question 6

what does the Val/Val polymorphism of COMT do in the brain

Answer 6

produces an enzyme that is more effective at metabolizing DA
leads to lower PFC DA levels vs the Met/Met version

Question 7

what else is the Val/Val COMT gene associated with

Answer 7

poorer cognitive performance
may exacerbate cog dysfunction in schizophrenia

Question 8

what is the glutamate hypothesis of schizophrenia

Answer 8

non competitive NMDA antagonists can induce psychotic symptoms and cognitive deficits resembling schizophrenia in healthy individuals

Question 9

what does the degeneration of glutaminergic PFC/hippocampal neurons do in the brain

Answer 9

disrupts the functioning of these cells and leads to less glutamate transmission

Question 10

what is the broad glutamate hypothesis

Answer 10

schizophrenia is caused by decreased glutamate transmission

Question 11

what do studies using primate/rat models show regarding acute or repeated PCP

Answer 11

decreased DA levels in the PFC
cog deficits on PFC dependent tasks

Question 12

how does the use of PCP cause symptoms

Answer 12

imbalance of DA transmission in PFC (too little) and striatum (too much)

Question 13

what does the PCP model in animals show that is similar to schizophrenia

Answer 13

the model encompasses some of the positive and negative symptoms of schizophrenia

Question 14

what can perturbed glutamate contribute to

Answer 14

increases in mesolimbic DA and reduced PFC DA transmission

Question 15

what do descending PFC projections affect

Answer 15

both DA pathways

Question 16

where do excitatory PFC projections synapse

Answer 16

directly onto mesocortical DA neurons (PFC excites these cells)

Question 17

where else do PFC input to

Answer 17

VTA GABA neurons that in turn synapse onto mesolimbic DA neurons (PFC activity can inhibit these cells)

Question 18

what can reduced PFC glutamate do to DA release

Answer 18

reduce DA release in PFC further causing more negative cog symptoms
also provide less excitation on VTA GABA neurons which could lead to excess NAc DA release causing more positive symptoms

Question 19

what can NMDA antagonists that induce psychosis/cog deficits do to activity of GABAergic interneurons

Answer 19

can reduce the activity of the GABAergic interneurons (and produce a ‘noisy’ cortex)

Question 20

where do NMDA receptors reside

Answer 20

on pyramidal cells and GABA interneurons

Question 21

what can lower doses of PCP/ketamine do to NMDA receptos

Answer 21

block them
they have a greater effect on interneurons to reduce their activity
this can cause disinhibitory increases in pyramidal neuron firing

Question 22

what is the net effect of PCP/ketamine on cells

Answer 22

disruption of the excitatory/inhibitory balance, with reduced signal combined with aberrant hyperactivity (aka noise)

Question 23

animal model of schizophrenia pharmacologically

Answer 23

high doses of amphetamine
produces stereotyped behaviours like sniffing/licking/gnawing like the compulsive repetitions of behaviour seen in schizophrenia
often used to identify potential antipsychotic drugs but does not reproduce the negative/cog symptoms very well

Question 24

neurodevelopment method to induce schizophrenia like symptoms

Answer 24

early insults (poor diet, viral infections, stressors, hypoxia) to pregnant rodents or young offspring induce neural/behavioural abnormalities later in life

Question 25

lesion method to induce schizophrenia like behaviours

Answer 25

neonatal ventral hippocampal lesion
well characterized model where a single, early life defect produces physiological/behavioural abnormalities in adulthood
show beh changes in adolescence that reflect symptoms of schizophrenia
neg/cog deficits show in early adulthood and can be potentiated by stress