Date of Award

2010

Degree Type

Thesis

Degree Name

Master of Science

Program

Neuroscience

Supervisor

Dr. L. Stan Leung

Abstract

It was hypothesized that neuronal inhibition in the hippocampus is altered following repeated seizures in immature rats. To test this, seizures were induced by i.p. injections of GABAb antagonist CGP56999A in postnatal day (PND) 15 Long-Evans rats. Following surgery at ~PND 50 to implant electrodes and cannulae into four locations within the CAl area of the hippocampus, awake adult (PND 60+) rats were tested on paired pulse responses to auditory stimuli and direct electrical stimulation of the hippocampus. Gating of the auditory evoked potential and the electrically induced population excitatory postsynaptic potential was measured by the ratio of the 2nd pulse response to the response of the single unpaired pulse. Seizure compared to Control rats had significantly decreased auditory gating at 500 ms interpulse

interval (IPI) and gating of electrical stimuli at 30 - 500 ms IPI. In tests of paired electrical stimuli, direct hippocampal infusion of CGP56999A disrupted the gating at long-latency (200­ 500 ms) in Control rats but not Seizure rats. Administration of diazepam and picrotoxin disrupted early gating of the electrically induced responses, but the effect was not different between Control and Seizure rats. In conclusion, repeated seizures in early life induced a decrease in inhibition, in particular the late GABAb receptor-mediated inhibition, in the adult hippocampus of behaving animals.

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