Our research focuses on epilepsy, neuroplasticity, and stem cell replacement therapy for temporal lobe epilepsy.
The Naegele lab is broadly interested in neural circuit repair and anti-convulsant strategies based on Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and stem cell transplantation. One of the main projects is focused on studying mouse or human embryonic GABAergic progenitors after transplantation into the hippopcampus of mice with chemoconvulsant-induced temporal lobe epilepsy. The high motility and plasticity of GABAergic interneuron progenitors enables them to migrate extensively within mature brain circuits and rewire neural circuitry after they are transplanted. We discovered that GABAergic progenitors from mouse and human pluripotent stem cells mature and synaptically integrate into the adult hippocampus of mice (in collaboration with Laura Grabel and Gloster Aaron’s labs). We showed that GABAergic progenitor’s harvested from mouse embryo’s can suppress spontaneous seizures in the mouse pilocarpine model of temporal lobe epilepsy (Henderson, Gupta et al. 2014). We use a range of approaches to investigate the mechanisms for neural stem cell integration into neural circuitry, including: electrophysiology, optogenetics, retroviral labeling, and continuous 24/7 video-electroencephalographic recordings. We routinely assess neurodegenerative changes and axonal sprouting using a range of histological and immunohistochemical approaches. Our well-equipped behavioral core and expertise in mouse behavioral testing enables us to examine spatial memory deficits, anxiety, depression, and sociability in mice after transplantation, to evaluate efficacy of stem cell therapies. We have expertise in multiple epilepsy models in mice including: the audiogenic, kainic acid, pilocarpine models, and tuberous sclerosis models (collaborations with labs of Paul Lombroso and Angelique Bordey, Yale University).