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Using In-vivo Two Photon Microscopy to Investigate the Dentate Gate Hypothesis


The most common form of focal epilepsy in adults is mesial temporal lobe epilepsy (mTLE). Evidence points to the hippocampal formation as a key site of epileptogenesis of mTLE, but its mechanisms remain unknown. The dentate gate hypothesis has been a major mechanistic concept in epilepsy for over 20 years which posits that the sparse firing of the dentate gyrus acts as a ‘gate’ that prevents overexcitation of hippocampal circuits that lead to epilepsy. Using in vivo two-photon microscopy and surgical implantation of a chronic cranial imaging window, we were able to study the network activity within the hippocampus in awake mice. Consistent with the dentate gate hypothesis, we found increased hyperexcitability in the dentate gyrus of epileptic mice using a status epilepticus (SE) model in which SE was induced at 6 weeks of age or older. Surprisingly, mice induced with SE at 3 weeks of age did not develop hyperexcitability. The results of this study will be used to further study the pathophysiological and electrophysiological differences between younger and older mice induced with SE.

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