Epilepsy is a common neurological disorder that strikes about 1% of the world population. It is caused by excessive neuronal activity characterized by seizures, which are abnormal and uncontrolled discharges of action potentials. Considering the growing number of new cases of epilepsy in children and that is drug-resistant epilepsy, better understanding the pathogensis of epilepsy is in critical need for the development of new therapeutic intervention and remediation of psychomotor retardation associated with this disease.
40% of all epilepsy is mostly caused by mutations in ion channels which generate electrical current by mediating the movement of ions across the plasma membrane. Since ion channels are essential for generation and modulation of action potentials and synaptic transmission, we investigate how novel epilepsy-associated mutations disrupt their biophysical properties and localization, and ultimately contribute to epilepsy by affecting action potentials and synaptic transmission.
60% of all epilepsy is caused by non-genetic factors and often associated with initial insults into the brain including traumatic brain injuries (which leads to chronic neuronal inactivity) or status epilepticus (extreme neuronal activity). After certain latency period, these insult-induced chronic activity changes ultimately lead to persistent neuronal hyperexcitability. This process is hypothesized to be caused by the failure of “homeostatic plasticity”, dynamic regulatory mechanisms by which neurons maintain their action potential firing and synaptic strength within physiological limit in response to constant neuronal activity changes. However, the molecular basis of this important plasticity has yet to be elucidated. We investigate the cellular and molecular mechanisms underlying homeostatic plasticity.
We employ interdisciplinary approaches including primary neuronal culture, live and fixed microscopy, biochemistry, and electrophysiology. In particular, we are developing mouse models in which neuronal activity can be chronically blocked or activated, and hope to use these models to understand the role of homeostatic plasticity in epilepsy.