Project 4 — Laminar organization of cortical functional connectivity in monkeys
This project will establish the role of layer 3 neurons in the cognitive deficits in schizophrenia.
Carl R. Olson, PhD
Professor, Center for the Neural Basis of Cognition, Carnegie Mellon University
Carol L. Colby, PhD
In tasks requiring attention and working memory, prefrontal and parietal cortex exhibit functional connectivity in the form of oscillatory phase-locking. Project 4 will test the general hypothesis that phase-locking depends on direct connections between the two areas originating from neurons in layer 3. By monitoring electrical activity simultaneously at fine intervals from the cortical surface to the white matter, while monkeys engage in working memory (Aim 1) and attention (Aim 2), the experiments will test the specific prediction that signs of functional connectivity are maximal in layer 3. By monitoring the electrical activity of identified projection neurons and by examining the impact of blocking projections between the two areas, the experiments will test the specific prediction that direct projections are critical for functional connectivity (Aim 3). Results obtained in Project 4 will have direct relevance to the Central Hypothesis regarding the origin of cognitive deficits in schizophrenia. This hypothesis states that cognitive deficits arise because pathological changes in layer 3 pyramidal cells interfere with functional connectivity between prefrontal and parietal cortex. Projects 1-3 will focus on the properties of layer 3 pyramidal cells in the healthy brain and in schizophrenia. Project 5 will focus on functional connectivity in the healthy brain and in schizophrenia as measured with coherence and causality analyses. The unique contribution of Project 4 will be to link these domains of inquiry by establishing the role of layer 3 neurons in functional connectivity as assessed with coherence and causality analyses.
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Silvio O. Conte Center for Translational Mental Health Research
Funded by the National Institute of Mental Health (MH103204)