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Exam 3
What is impaired reality testing?
Agents internal perception does not match up with external reality
What neurological abnormalities are associated with the dominant-negative form of DISC-1?
alteration in GABAergic interneuron signaling
Decreased parvalbumin (PVB) expression
Swelling of the lateral ventricles
enhanced D2R function
decreased extracellular DA in frontal cortex
What behavioral endophenotypes are associated with DN-DISC-1?
Impaired reality testing
Impaired social learning
Perseverance
What is the normative function of DISC-1?
Involved in many intracellular developmental and synaptic processes
What function does the insular cortex generally serve?
gustatory cortex, associated with taste responsivity
What evidence do we have that implicates the VTA > IC circuitry in impaired reality testing?
Loss of VTA > IC dopaminergic tone is sufficient to yield impaired reality testing in wild-type subjects
DR1-mediated excitation of GABA in IC is lost > uncontrolled firing when stimulated
Inactivation of VTA > IC DA significantly increased lick burst size for unflavored water
What evidence is there to suggest that DN-DISC1 leads to a loss of functional connectivity between the midbrain and the frontal-cortical regions? How might this predispose an individual to hallucinations?
DISC-1 compared to wild type mice had significantly lower number of cells projecting from VTA to IC > decrease in functional connectivity between midbrain and frontal cortex
Significantly reduced colonized cells (virus + DA) in DISC-1 indicating reduced VTA > IC DA connectivity
may lead to abberant internal perception generated by an overreliance on prior knowledge at expense of incoming sensory experience > adaptive strategy to deal witht he issue
DR1-mediated exicitation of GABA in IC ilost > unchecked firing response to stimuli = abnormally strong internal perception s
