Hypofunction of cortico-basal ganglia circuits has been hypothesized to underlie some of the debilitating cognitive deficits and negative symptoms that are seen in schizophrenic patients. Antipsychotics are thought to mediate some of their therapeutic effects by normalizing this activity. However, the precise cell populations and the molecular changes involved in this response are still not fully understood. In Project 2 of this Conte center application, we hypothesize that cell-type specific changes in neurons projecting from the frontal cortex to the basal ganglia occur in response to typical and atypical antipsychotic drugs. To test this hypothesis, we will make use of a novel mRNA translational profiling approach.
In Aim 1 of this project, we will perform these studies on two distinct cortico-striatal cell populations we have targeted genetically.
In Aim 2, we will characterize two newly generated mouse lines that may give us translational profiling access to two additional cortico-striatal cell populations. Finally, in Aim 3, in collaboration with the other projects of this center, we will perform a functional analysis of molecules identified in our translational profiling studies of Aims 1 and 2.
to public health: Schizophrenia is a debilitating psychiatric disorder affecting - 1 % of the population. New therapeutic treatments for schizophrenia are needed. Project 2 will contribute to a more complete understanding of the cellular and molecular actions of antipsychotic drugs through biochemical studies of the actions of these drugs in specific populations of nerve cells.
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