Perception, attention, working memory, and explicit learning represent a continuum of information processing in which there are major deficits in schizophrenia. These deficits may reflect abnormalities in the molecular and/or physical architecture mediating activity-dependent neural plasticity and are likely to be especially prominent in highly plastic, nodal regions for information processing. One neural system which is known to play important roles in sensory gating phenomena, novelty detection and salience, and verbal and spatial learning is composed of the hippocampus, prefrontal cortex, and nucleus accumbens. At the cellular level early information processing events associated with sensory gating and novelty detection are electrophysiologically mediated, without long lasting molecular or structural changes. With learning of environmental stimuli, there are long lasting modifications of synaptic neurotransmission that are mediated by post-synaptic neuronal changes in gene expression, pre-synaptic axon terminal remodeling, increases in post synaptic densities and dendritic spines, and associated changes in the neuronal cytoskeleton. In turn, these changes modify earlier information processing events. Our central hypothesis is that selective cellular and molecular mechanisms that mediate sensory gating, learning and activity-dependent plasticity are abnormal in schizophrenia. This will be investigated in human postmortem tissues from well-characterized subjects with schizophrenia and matched, healthy controls as well as mice that have undergone genetic, behavioral and electrophysiological manipulations relevant to schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
1P50MH064045-01
Application #
6553522
Study Section
Special Emphasis Panel (ZMH1)
Project Start
2001-09-15
Project End
2006-07-31
Budget Start
Budget End
Support Year
1
Fiscal Year
2001
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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