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. Author manuscript; available in PMC: 2010 Sep 1.
Published in final edited form as: Eur J Neurosci. 2009 Sep 4;30(6):1036–1055. doi: 10.1111/j.1460-9568.2009.06896.x

FIG. 11. KA-induced gamma oscillations and CA1 cell death in CA3-NR1 KO mice.

FIG. 11

Depiction of how genetic deletion of CA3-NR1 influences CA3-CA1 network activity (blue) and, upon KA administration, undergoes CA1 neurodegeneration (pink). Post-adolescent NR1 elimination in CA3 pyramidal cells (GLU cells) diminishes their action potential firing, thereby reducing the firing of CA1 interneurons (GABA cell) while CA1 pyramidal cell activity is maintained by reduced feed-forward inhibition. Simultaneously, CA3-NR1 deletion abnormally enhances sharp wave-ripple (SPW-R) activity in CA3. An intermediate dose of kainic acid (KA, 20 mg/kg, i.p.) facilitates GABA release, thereby eliciting 30-50 Hz gamma oscillations within 20 min, then evoking epileptic discharge-burst activity in the control animals (black arrow). However, this dose does not extend the epileptic discharges to the sustained epileptiform activity on the following days, and consequently, no cell death is observed in the control hippocampus. In contrast, KA-induced GABA release and gamma oscillations do not occur in area CA1 of the mutants, presumably due to reduced excitability of CA1 interneurons, and epileptic discharges are instead exacerbated, along with an enhancement of SPW-R activity (red arrow). A presynaptic GABA release enhancer, DTX (blue arrow), has no effect on mutant SPW-R activity and seizure severity after KA administration. Remarkably, however, it assists in KA-induced GABA release which maintains the integrity of the CA1 GABAergic network, thereby preserving gamma oscillations, suppressing epileptiform activity, and further protecting mutant CA1 from KA-induced excitotoxicity. These results suggest that KA-induced GABA release may prevent epileptic discharges from transforming the sustained epileptiform activity and deteriorating GAD67-positive cells, which results in no neurodegeneration of CA1 neurons. Overall, the emergence of KA-induced gamma oscillations predicts good prognosis against KA-induced hippocampal excitotoxicity in mice. Question mark denotes putative action/change.