Basic Science Research

SUNY Downstate Medical Center has internationally-recognized expertise in research involving the basic mechanisms of epilepsy. While a substantial effort is devoted to studying neuronal excitability, the primary focus at this institution is on the mechanisms which oppose and thus regulate excitability, namely GABAergic inhibition. When activity proceeds in a focused and coherent manner, the process is associated with normal behavior, healthy cortical development, and normal learning and memory formation. When the process becomes deranged and goes unchecked, the result is seizure activity and epilepsy. Consequently, the cellular and synaptic mechanisms of inhibition are central to understanding the processes leading to excitotoxicity and epileptogenesis, and their exploration is a necessary step in developing clinical therapies for pathogenic states resulting from neuronal hyperexcitability.

The areas of investigation include:

• the structure of the GABAergic inhibitory circuit and its functional   relationships in the neocortex and hippocampus

• transmitter modulation of hippocampal neuronal network and
  their role in the mechanisms of epileptogenesis

• modulation of hippocampal circuits by neuroactive steroids and its   possible relevance for the premenstrual syndrome, catamenial   epilepsy, and seizure susceptibility

• the maturation of GABA-mediated inhibition

• modeling of electrophysiological processes pertinent to epilepsy

• the role of gene expression in the pathophysiology of neuronal   disorders, particularly stroke and epilepsy

These studies mainly involve the use of biophysical approaches, such as voltage clamping and patch clamping applied to brain slices. A number of complementary techniques are also being brought to bear upon these issues, including molecular and computational methodologies. This work has been well-funded by the National Institutes of Health and the American Epilepsy Society.