The dopaminergic innervation of the prefrontal cortex is an important component of current hypotheses on the pathophysiology of schizophrenia. Unfortunately, the actions of dopamine in the cortex are not well understood, so we cannot envision a clear picture of how dopamine disturbances can result in symptoms. This field has a large number of inconsistent and often contradictory reports, with the actions of dopamine frequently characterized as inhibitory, excitatory or simply modulatory. We plan to test the hypothesis that dopamine in the prefrontal cortex sustains periods of depolarization (up states) during which synaptic activity is gated. The experiments will address: 1) whether dopamine cell activity is correlated with prefrontal cortical up states and whether inactivating the source of dopamine, the ventral tegmental area, eliminates or reduces up states; 2) whether dopamine cells and the prefrontal cortex enhance their synchrony in awake animals during conditions known to drive the dopaminergic projection; 3) whether dopamine can modulate plateau depolarizations resembling up states in a brain slice preparation; 4) whether activation of the mesocortical projection enhances metabolic activity in the prefrontal cortex; and 5) dopamine-glutamate interactions in prefrontal cortical slices obtained from animals with a neonatal ventral hippocampal lesion.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH057683-06A2
Application #
6687492
Study Section
Special Emphasis Panel (ZRG1-IFCN-4 (02))
Program Officer
Chen, Daofen
Project Start
1997-09-01
Project End
2007-05-31
Budget Start
2003-07-16
Budget End
2004-05-31
Support Year
6
Fiscal Year
2003
Total Cost
$331,641
Indirect Cost
Name
Albany Medical College
Department
Pharmacology
Type
Schools of Medicine
DUNS #
190592162
City
Albany
State
NY
Country
United States
Zip Code
12208
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