Neuronal Excitability and Disease Research

The process of neuronal excitability is supported by a set of unique proteins called ion channels that allow the passage of specific ion species across different cellular compartments. The coordinated actions of diverse ion channels set the excitatory and inhibitory (E/I) balance to allow the transfer of information within neural circuits, which ultimately support all aspects of memory and behavior. The primary focus of our lab is to determine the cellular, molecular, and physiological phenomenons that orchestrate the functions of different ion channels to support the E/I balance in normal brain physiology and the mechanisms that induce a shift in the E/I operation in neurobiological disease states such as Aging, Epilepsy, and Dementia. Towards this, we use a diverse spectrum of methodologies from cell culture preparations, molecular biology, and analytical biochemistry tools to brain slice patch clamping, electrophysiology modalities, computational tools, epi-fluorescence, and advanced super-resolution microscopy approach.

Epilepsy Research Theme: 

Epilepsy is characterized by recurrent unprovoked seizures resulting in the abnormal, spontaneous, and synchronized high-frequency firing of a population of neurons leading to learning disabilities, social interaction, and psychological problems. Epilepsy affects approximately 1-2% of the population worldwide and is considered one of the most common neurological disorders. Among different types of epilepsy, temporal lobe epilepsy (TLE) accounts for 60-70% of epilepsy cases worldwide and is regarded as the most prevalent form of epilepsy. Notably, TLE is difficult to treat effectively, with one-third of patients showing treatment-resistant intractable TLE recurrent seizures. Our lab’s research interests are understanding the pathophysiological mechanisms contributing to the generation of recurrent epileptic seizures in TLE. We are focussing on the contribution of specific ion channel proteins in the aberration/plasticity of intrinsic and synaptic excitability mechanisms in TLE.

Aging and Dementia Research Theme:

Normal and pathological aging is known to cause structural, chemical, and physiological changes in the hippocampus and its principal pyramidal neurons. This is reflected as difficulties in acquiring hippocampus-dependent episodic, spatial, and cognitive tasks that are well documented through studies on aged humans and also effectively represented in aged rodent and rabbit experiments. Notably, the principal pyramidal neurons of the hippocampus, widely known for involvement in episodic, spatial, and fear memory acquisition, show a dramatic change in the E/I equilibrium leading to alterations in the synaptic integration and intrinsic excitability properties. In our lab, we identify the ionic and cellular mechanisms that induce this E/I shift in the aging brain pyramidal neurons focussing on calcium and potassium permeable ion channels.