A plethora of evidence has implicated the improper functioning of the prefrontal cortex in the pathophysiology of schizophrenia. While numerous findings have described a role for monoaminergic and cholinergic projections to the prefrontal cortex in the cognitive functions associated with this region, the extent of the involvement of the most prevalent prefrontal cortex afferents, namely those projections that contain glutamate as their neurotransmitter, in mnemonic, attentional, and other associative functions of the prefrontal cortex has not been well characterized. Considering that a number of recent findings are suggestive of glutamatergic abnormalities in schizophrenia, it is imperative that more be learned about the role of glutamate receptors in cognitive functions that are relevant to schizophrenic symptomatology. The research proposed in this request for an Independent Scientist Award (K02) involves characterizing the contribution of glutamate receptors in regulating those associative functions of the prefrontal cortex that are relevant to the pathophysiology of schizophrenia. This award will allow the applicant to devote maximal effort to the above research objectives which entails receiving appropriate training in order to establish in her laboratory behavioral paradigms that have direct relevance to different aspects of the cognitive dysfunctions associated with schizophrenia and that are analogous to clinical tests at which patients with schizophrenia show an impairment. Considering that the present mode of therapy for schizophrenia, i.e., treatment with antidopaminergic drugs, does not effectively treat cognitive deficits associated with this disorder, an understanding of the neurochemical basis of associative functions of the prefrontal cortex will help in the development of novel pharmacotherapeutic strategies for the treatment of schizophrenia.
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