The proposed renewal of our Conte Center builds on a foundation of joint discovery and infrastructure directed at understanding neural substrates of schizophrenia. Our progress arises from applying diverse basic and clinical neuroscience perspectives that have probed anatomic, physiologic, neuropathologic, and genetic integrity of information processing in patients and animal models. The clinical projects have characterized the nature and extent of sensory processing deficits in schizophrenia, while the animal model projects have illuminated basic mechanisms of stimulus processing. Within the stimulus processing cascade that we examined, the clinical studies revealed that patients had robust abnormalities in perceptual encoding and detection of deviance. Furthermore, our postmortem studies discovered abnormalities in the expression and function of candidate genes that are mechanistically linked to glutamatergic neurotransmission in critical neural circuitry for signal detection and encoding. These data leads us to focus efforts onto investigating the neurobiological mechanisms of deviance detection in schizophrenia as the central theme for the proposed renewal application. This central hypothesis will be examined with converging methodologies in humans and rodents. The Center will be organized into seven Projects: 0001. Electrophysiology;0002. fMRI;0007. Molecular;0003. Signaling; 0008. Animal Electrophysiology;0009. Cellular;0010.Computation. Two Cores will support the Projects: Core A Coordination and Core B Data and Biostatistics. The proposed CCNMD capitalizes on the collaborative expertise of investigators and resources at the University of Pennsylvania for conducting this challenging interdisciplinary translational research. In addition to advancing its scientific agenda, the Center will be an educational resource for faculty, fellows, residents, graduate and undergraduate students. It will also be a clinical and educational resource for the community including individuals with schizophrenia, their families and care providers.
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