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Roles Of Mtorc1 And Mtorc2 In Epilepsy And Network Changes Induced By Pten Loss, Erin R. Cullen

Graduate College Dissertations and Theses

Gene variants that hyperactivate the mTOR signaling pathway are a major cause of treatment-resistant epilepsy. The mTOR pathway influences neuron function through two distinct complexes, mTORC1 and mTORC2. Pten loss of function (LOF) hyperactivates both mTOR complexes, and is thus a useful model for testing the effects of independent mTORC1 or mTORC2 hyperactivity on epilepsy and underlying neuropathology. Here, we evaluated the impact of genetic inactivation of the mTOR complexes in two mouse models of Pten LOF-driven epilepsy. In a germline GFAP-driven Pten LOF model targeting neurons in the dentate gyrus and cerebellum, a mild epilepsy phenotype was not rescued …