Ion Channel Trafficking at the Axon Initial Segment and Neural Excitability

2015 Seed Grant
Michael Hoppa, Ph.D.
Dartmouth College

Over 65 million people worldwide have epilepsy and suffer from debilitating seizures. Seizures result from clusters of neurons in a circuit to fire synchronously as the result of a lowered excitability threshold. Although the susceptibility for becoming epileptic increases with age, we have little understanding about why this threshold for electrical activity weakens to a pathological state. The axon initial segment is a master integrator switch in the neuron that initiates firing and harbors many unique proteins associated with epilepsy making it a prime area for research. We have devised several quantitative optogenetic approaches to specifically measure initial segment function in the context of neuronal plasticity and epileptogenesis. Under this experimental regime we will gain an understanding of a critical piece of novel cellular physiology that could uncover new targets for therapeutic approaches to combat and prevent epilepsy.