Emeritus Professor
Ph.D. Southern California

Hormonal regulation of GABA_A receptor, brain activity and sleep

Computational modeling of biological systems

Research

The goal of our current research is to clarify how thyroid hormones influence the adult mammalian brain. During growth and development, hormones from the thyroid gland enter many cell types (including brain cells) and alter protein synthesis. In adulthood, the cellular metabolic rate is accelerated by thyroid hormones entering cells of many tissues, but not in the brain. However, some of the potentially most debilitating complications of thyroid glandular disease are due to neurological disorders, ranging from anxiety and sleep problems to seizures or coma.

Our evidence indicates that thyroid hormones may bind to and influence the function of brain GABAa receptors. (GABAa receptors on the outside of neuronal membranes are responsible for cellular effects of the brain’s major inhibitory neurotransmitter, gamma-aminobutyric acid or GABA.) Current experiments are determining the effects of thyroid hormones on GABAa receptor binding, the subsequent cellular response, and the resultant electroencephalogram (brain waves which change with sleep or seizures).

These studies are designed to determine the biological significance of a brain action of thyroid hormones that more closely resembles the action of a neurotransmitter than it does the typical action of thyroid hormones in other tissues.

More recently, our interests have expanded to computational modeling of biological systems, including abstract theoretical models of brain function (with Dawei Hong) and testing the predictions of molecular dynamics simulations of the GABA_A  receptor (with Grace Brannigan).