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.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…