Date of Award


Degree Type


Degree Name

Master of Science


Pharmacology and Toxicology


Dr. L. Stan Leung

Second Advisor

Dr. Richard S. McLachlan

Third Advisor

Dr. Michael Poulter


It was hypothesized that dendritic paired-pulse inhibition in hippocampal CA1, in particular at a long-latency typical of GABAs-receptor mediated inhibition, is disrupted in rats following early-life seizures. To test this, homo- and hetero- synaptic paired-pulse responses in CA1, following CA3 and medial perforant path (MPP) stimulation that excited the proximal and distal apical-dendrites respectively, were recorded -30-65 days following early-life seizures. Two models of early-life seizures were used on male Long- Evans rats: (1) intraperitoneal injection of GABAb receptor antagonist CGP56999A on post-natal day (PND) 15 induced brief, repeated limbic seizures lasting 8-24 hr, and (2) 9 episodes of seizure activity induced by hyperthermia (3 times per day at 4 hr intervals) on PND 13-15. When recorded -30 or -65 days after CGP56999A-treatment, rats showed no long-term effect on paired-pulse responses as compared to age matched controls, except for a decrease in homosynaptic CA3-evoked paired-pulse facilitation recorded in the CA1 mid-apical dendritic layer at 20 ms interval pulse interval (IPI). In contrast, at -PND 65 rats treated with repeated hyperthermia seizures showed a decrease in heterosynaptic (CA3 then MPP stimulus-evoked) paired-pulse inhibition at the distal apical CA1 dendrites. Additionally, homosynaptic paired-pulse inhibition at 20-80 ms IPI recorded in the mid-apical dendritic layers of CA1 was decreased in hyperthermia-treated rats compared to control rats. These results suggest that long-term alterations in dendritic excitation and inhibition can occur following early-life seizure activity.



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