The interactions among the prefrontal cortex, hippocampus and dopaminergic systems are thought to play a role in schizophrenia. However, the nature of such interactions from a physiological perspective are not yet fully understood. Establishing how a hippocampal deficit impacts on physiological measures of prefrontal neuron activity and how dopamine modulates these interactions may provide a significant contribution towards establishing a comprehensive animal model of this devastating disorder. In this proposal, plans are presented to assess the impact of a number of manipulations in the hippocampal afferents to prefrontal cortical neurons intracellularly recorded in vivo: 1) determining the input responsible for the transitions to the active periods in prefrontal cortical neurons exhibiting a slow oscillation in their membrane potential and cell firing; 2) establishing the role of hippocampal afferents on such oscillations and their source input by assessing the effects of hippocampal stimulation and by performing similar experiments in animals with a hippocampal lesion; 3) assessing the effects of a neonatal hippocampal lesion on these interactions in adult animals as an initial attempt of testing the hypothesis of a developmental hippocampal disturbance resulting in hypofrontality; 4) testing the effects of rearing animals in social isolation on these interactions, with the aim to determine the actions of an environmentally-induced brain deficit that in many respects exhibits alterations resembling schizophrenia; and, 5) determining the glutamate receptor subtype involved in hippocampal-prefrontal interactions by studying the actions of glutamate receptor agonists and antagonists on synaptic responses in prefrontal cortical cells recorded in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH057683-04
Application #
6185815
Study Section
Cognitive Functional Neuroscience Review Committee (CFN)
Project Start
1997-09-01
Project End
2002-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
4
Fiscal Year
2000
Total Cost
$191,473
Indirect Cost
Name
Albany Medical College
Department
Pharmacology
Type
Schools of Medicine
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12208
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Dilgen, Jonathan; Tejeda, Hugo A; O'Donnell, Patricio (2013) Amygdala inputs drive feedforward inhibition in the medial prefrontal cortex. J Neurophysiol 110:221-9

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