@article {YuENEURO.0003-16.2016, author = {Lily M. Y. Yu and Denis Polygalov and Marie E. Wintzer and Ming-Ching Chiang and Thomas J. McHugh}, title = {CA3 synaptic silencing attenuates kainic acid induced seizures and hippocampal network oscillations}, elocation-id = {ENEURO.0003-16.2016}, year = {2016}, doi = {10.1523/ENEURO.0003-16.2016}, publisher = {Society for Neuroscience}, abstract = {Epilepsy is a neurological disorder defined by the presence of seizure activity, manifest both behaviorally and as abnormal activity in neuronal networks. An established model to study the disorder in rodents is the systemic injection of kainic acid, an excitatory neurotoxin which at low doses quickly induces behavioral and electrophysiological seizures. While the CA3 region of the hippocampus has been suggested to be crucial for kainic acid induced seizure, due to its strong expression of kainate glutamate receptors and its high degree of recurrent connectivity, the precise role of excitatory transmission in CA3 in the generation of seizure and the accompanying increase in neuronal oscillations remains largely untested. Here we employ transgenic mice in which CA3 pyramidal cell synaptic transmission can be inducibly silenced in the adult to demonstrate CA3 excitatory output is required for both the generation of epileptiform oscillatory activity and the progression of behavioral seizures.Significance Statement: The prevalence of epilepsy as a clinical concern has inspired the investigation of the mechanisms of seizure generation in animal models. A common model in the mouse is the injection of the neurotoxin kainic acid (KA). However given the ability of KA to alter the activity of many cell types and circuits, it remains unclear how KA leads to seizure. Here we demonstrate that synaptic transmission from CA3 pyramidal cells in the hippocampus is necessary for KA induced seizure activity, both behaviorally and physiologically. This establishes CA3 as the key locus for KA induced pathophysiology and will aid in designing better models and interventions to understand and control seizures.}, URL = {https://www.eneuro.org/content/early/2016/02/10/ENEURO.0003-16.2016}, eprint = {https://www.eneuro.org/content/early/2016/02/10/ENEURO.0003-16.2016.full.pdf}, journal = {eNeuro} }