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 attenfion (Aim 2), the experiments will test the speciflc predicfion that signs of funcfional 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 deflcits in schizophrenia. This hypothesis states that cognifive 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 funcfional connectivity in the healthy brain and in schizophrenia as measured with coherence and causality analyses. The unique contribufion 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.

Public Health Relevance

This project will establish the role of layer 3 neurons in the cognitive deflcits in schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
1P50MH103204-01
Application #
8816253
Study Section
Special Emphasis Panel (ZMH1-ERB-L (01))
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$249,013
Indirect Cost
$38,149
Name
University of Pittsburgh
Department
Type
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Moyer, Caitlin E; Shelton, Micah A; Sweet, Robert A (2015) Dendritic spine alterations in schizophrenia. Neurosci Lett 601:46-53
Hu, Wei; MacDonald, Matthew L; Elswick, Daniel E et al. (2015) The glutamate hypothesis of schizophrenia: evidence from human brain tissue studies. Ann N Y Acad Sci 1338:38-57