The normal functional architecture of the primate prefrontal cortex, including its connections with other cortical and subcortical regions, is examined using the macaque monkey as a model system for the human brain. Within these circuits, the expression and cellular localization of specific gene products, and how these change in an activity-dependent fashion, are investigated. The electrophysiological properties of intrinsic prefrontal cortical circuits are studied using an in vitro slice preparation.
Based on the results of other lines of investigation in the Lewis Lab, hypotheses are generated regarding the elements of neural circuitry that are dysfunctional in schizophrenia. These hypotheses are then tested in postmortem human brain specimens from subjects with schizophrenia.
Mouse genetic models are used as “proof of concept” tests of the cause-effect relationships among the neural circuitry alterations observed in schizophrenia. The goal of these studies is to define the pathogenic mechanisms and pathophysiological processes that give rise to the cognitive deficits of schizophrenia.
The postnatal development of primate prefrontal cortical circuitry is characterized, with special emphasis placed on maturational events, such as synaptic pruning, which occurs during adolescence. The timing and specificity of these processes are examined for their possible contribution to the emergence and refinement of the types of cognitive abilities that are disturbed in schizophrenia.
The primate model system is used to assess the influence of psychotropic medications on the neural circuits of interest.
TARGETS FOR INTERVENTIONS
Findings from the neural circuitry studies of schizophrenia are used to identify potential targets for novel therapeutic interventions that are examined in Phase II clinical trials.
Laboratory of David A. Lewis, MD
Researching the neural circuitry of the prefrontal cortex and related brain regions, and the alterations of this circuitry in schizophrenia.
© 2017 University of Pittsburgh
Western Psychiatric Institute and Clinic 3811 O’Hara Street Pittsburgh, PA 15213-2593
University of Pittsburgh Department of Psychiatry W1651 Biomedical Science Tower 203 Lothrop Street Pittsburgh, PA 15213-2593