Project Summary

Claudia Schmauss, M.D. (Independent Investigator 2004) of Columbia University, notes that attention deficits are prominent features of schizophrenia and are thought to result from abnormal neuronal activity in the prefrontal cortex (PFC), an anatomic structure critically involved in “top-down” conceptual cognitive processing. Although the mesocortical dopaminergic system
has been implicated in the control of these cognitive processes, the role of dopamine subtypes in attention is not fully understood. Using a mouse model, Dr. Schmauss studied the performance of mice lacking dopamine D2 and D3 receptors in a cognitive task that tests ability to acquire rules, maintain and shift attentional sets, and requires flexibility to respond to reversal conditions, and found that D2 mutants had significant deficits in rule learning. She will now test whether the extent of the neuronal activation in the mPFC in response to the attention-requiring test is modulated by D2 and D3 receptors and whether it is inversely correlated with the error rates by performing an assessment of the number of neurons that express task-induced FOS-immunoreactivity in the mPFC in 3 types of mice. She will also test whether the longer response latencies of D3 mutants are due to decreased reward expectation. She believes these studies will provide information into the different roles of D2 and D3 receptors, the main targets of anti-psychotics.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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