Inhibitory control of sensory gating in a computer model of the CA3 region of the hippocampus |
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Authors: | Karen A Moxon Greg A Gerhardt Maria Gulinello Lawrence E Adler |
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Institution: | (1) Drexel University, School of Biomedical Engineering, Science and Health Systems, Philadelphia, PA 19104, USA, US;(2) University of Kentucky Chandler Medical Center, Department of Anatomy & Neurobiology, Lexington, KY 40536, USA, US;(3) Department of Physiology, State University of New York at Brooklyn, Brooklyn, NY 11203 USA, US;(4) University of Colorado Health Sciences Center, Department of Psychiatry, Denver, CO 80262, USA, US |
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Abstract: | A model of the CA3 region of the hippocampus was used to simulate the P50 auditory-evoked potential response to repeated
stimuli in order to study the neuronal circuits involved in a sensory-processing deficit associated with schizophrenia. Normal
subjects have a reduced P50 auditory-evoked potential amplitude in response to the second of two paired auditory click stimuli
spaced 0.5 s apart. However, schizophrenic patients do not gate or reduce their response to the second click. They have equal
auditory-evoked response amplitudes to both clicks. When schizophrenic patients were medicated with traditional neuroleptics,
the evoked potential amplitude to both clicks increased, but gating of the second response was not restored or improved. Animal
studies suggest a role for septohippocampal cholinergic activity in sensory gating. We used a computational model of this
system in order to study the relative contributions of local processing and afferent activity in sensory gating. We first
compared the effect of information representation as average firing rate to information representation as cell assemblies
in order to evaluate the best method to represent the response of hippocampal neurons to the auditory click. We then studied
the effects of nicotinic cholinergic input on the response of the network and the effect of GABAB receptor activation on the ability of the local network to suppress the test response. The results of our model showed that
nicotinic cholinergic input from the septum to the hippocampus can control the flow of sensory information from the cortex
into the hippocampus. In addition, postsynaptic GABAB receptor activation was not sufficient to suppress the test response when the interstimulus interval was 500 ms. However,
presynaptic GABAB receptor activity may be responsible for the suppression of the test response at this interstimulus interval.
Received: 3 December 2001 / Accepted: 23 October 2002 / Published online: 28 February 2003
Correspondence to: K. A. Moxon (e-mail: karen.moxon@drexel.edu, Tel.:+1-215-8951959, Fax: +1-215-8954983)
Supported by USPHS, MH01245, MH58414, MH-50787, MH-01121, and research grants from the Department of Veterans Affairs and
the National Alliance for Research on Schizophrenia and Depression. |
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