Developing a Model of Naturalistic Focal Seizures
Penn collection
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Neuroscience and Neurobiology
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Neurology
Epilepsy
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Abstract
Epilepsy is the most common chronic neurologic disease, but still little is known about the underlying mechanisms of seizure initiation in epilepsy disorders. In vivo imaging of seizures in two-photon (2P) calcium imaging facilitates recordings of neuronal activity at a high spatial and temporal cellular resolution in awake, behaving experimental animals. The aim of this study is to develop a novel method to visualize focal seizure initiation in a mouse using in vivo 2P calcium imaging. To focally mimic the pathophysiology of Dravet Syndrome, the most common genetic epilepsy syndrome of childhood, an adeno-associated virus expressing Cre recombinase was locally injected into the primary somatosensory cortex to induce heterozygous deletion of the Scn1a gene encoding sodium channel subunit Nav.1.1. We found that focal heterozygous deletion of Scn1a may not be a powerful enough genetic lesion to induce a focal seizure, and that the viral injection may be causing local cell death. Future directions include optimizing the viral injection protocol to successfully induce a focal seizure. This project will help to better understand the underlying mechanisms of seizure initiation in hopes of improving treatments for Dravet Syndrome and other epilepsies.