Probing Synaptic Changes in a Novel Mouse Model of Severe Epilepsy with Nanoparticle-Enabled 3D Super-Resolution Imaging
Normal brain function requires a precise balance between excitation and inhibition. Too much excitation or too little inhibition can result in seizures or epilepsy. A protein family called GABAA receptors (GABAAR) mediates brain inhibition. A single mutation in the genes of the protein family can cause different kinds of epilepsy. We have made a mouse model carrying a mutation in a gene that causes a severe form of epilepsy known as Dravet Syndrome. The mice carrying this mutation had seizures and other neurodevelopmental abnormalities. This provides us a very useful window to understand the pathophysiology of epilepsy. We propose to use photoluminescent nanoparticles called quantum dots to perform 3D super-resolution tracking of the dynamic behaviors of this protein family in live neurons in the mutation-carrying mice. In combination with multiple molecular, biochemical, electrophysiological and behavioral approaches, we will determine the changes of GABAAR membrane dynamics, synapse formation, connectivity, plasticity as well as synaptic transmission of inhibitory neuronal circuit. We hope this study will bring us a step closer to finding a cure for epilepsy.