lecture 21 LOs Flashcards
what receptors in the PFC mediate working memory
PFC D1 but not D2
how can manipulating PFC DA D1 activity change baseline levels of performance
poor performance: extra D1 stimulation will improve functioning
good performance: D1 receptors antagonist impairs functioning
which receptors mediate congnitive flexibility
D1 and D2 receptors
what does supranormal stimulation of D1 or D2 do to cognitive flexibility
does not affect it
what does D4 receptor stimulation impair
set shifting
S shaped function
what does the Val/Val polymorphism of COMT do in the brain
produces an enzyme that is more effective at metabolizing DA
leads to lower PFC DA levels vs the Met/Met version
what else is the Val/Val COMT gene associated with
poorer cognitive performance
may exacerbate cog dysfunction in schizophrenia
what is the glutamate hypothesis of schizophrenia
non competitive NMDA antagonists can induce psychotic symptoms and cognitive deficits resembling schizophrenia in healthy individuals
what does the degeneration of glutaminergic PFC/hippocampal neurons do in the brain
disrupts the functioning of these cells and leads to less glutamate transmission
what is the broad glutamate hypothesis
schizophrenia is caused by decreased glutamate transmission
what do studies using primate/rat models show regarding acute or repeated PCP
decreased DA levels in the PFC
cog deficits on PFC dependent tasks
how does the use of PCP cause symptoms
imbalance of DA transmission in PFC (too little) and striatum (too much)
what does the PCP model in animals show that is similar to schizophrenia
the model encompasses some of the positive and negative symptoms of schizophrenia
what can perturbed glutamate contribute to
increases in mesolimbic DA and reduced PFC DA transmission
what do descending PFC projections affect
both DA pathways
where do excitatory PFC projections synapse
directly onto mesocortical DA neurons (PFC excites these cells)
where else do PFC input to
VTA GABA neurons that in turn synapse onto mesolimbic DA neurons (PFC activity can inhibit these cells)
what can reduced PFC glutamate do to DA release
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
what can NMDA antagonists that induce psychosis/cog deficits do to activity of GABAergic interneurons
can reduce the activity of the GABAergic interneurons (and produce a ‘noisy’ cortex)
where do NMDA receptors reside
on pyramidal cells and GABA interneurons
what can lower doses of PCP/ketamine do to NMDA receptos
block them
they have a greater effect on interneurons to reduce their activity
this can cause disinhibitory increases in pyramidal neuron firing
what is the net effect of PCP/ketamine on cells
disruption of the excitatory/inhibitory balance, with reduced signal combined with aberrant hyperactivity (aka noise)
animal model of schizophrenia pharmacologically
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
neurodevelopment method to induce schizophrenia like symptoms
early insults (poor diet, viral infections, stressors, hypoxia) to pregnant rodents or young offspring induce neural/behavioural abnormalities later in life
lesion method to induce schizophrenia like behaviours
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