Impaired hippocampal memory function and synaptic plasticity in experimental cortical dysplasia

Authors


Address correspondence to Fu-Wen Zhou, Department of Neurosurgery, University of Florida, 100 South Newell Drive, Room L2-100, Gainesville, FL 32610, U.S.A. E-mail: fuwen.zhou@neurosurgery.ufl.edu

Summary

Purpose:  Memory impairment is a common comorbidity in people with epilepsy-associated malformations of cortical development. We studied spatial memory performance and hippocampal synaptic plasticity in an animal model of cortical dysplasia.

Methods:  Embryonic day 17 rats were exposed to 2.25 Gy external radiation. One-month-old rats were tested for spatial recognition memory. After behavioral testing, short-term and long-term synaptic plasticity in the hippocampal CA1 region was studied in an in vitro slice preparation.

Key Findings:  Behavioral assessments showed impaired hippocampal CA1-dependent spatial recognition memory in irradiated rats. Neurophysiologic assessments showed that baseline synaptic transmission was significantly enhanced, whereas paired-pulse facilitation, long-term potentiation, and long-term depression of the field excitatory postsynaptic potential (fEPSP) slope at Schaffer collateral/commissural fiber-CA1 synapses were significantly reduced in the irradiated rats. Histologic observations showed dysplastic cortex and dispersed hippocampal pyramidal neurons.

Significance:  This study has shown that prenatally irradiated rats with cortical dysplasia exhibit a severe impairment of spatial recognition memory accompanied by disrupted short-term and long-term synaptic plasticity and may help to guide development of potential therapeutic interventions for this important problem.

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