My research program combines aspects of cellular, synaptic and network neuroscience by using advanced tools in cellular physiology, neuropharmacology, imaging and molecular biology to elucidate mechanisms regulating excitability. Ongoing research points to neurosteroids as a prime candidate in regulating the balance between excitation and inhibition. Cortical neurons possess unique properties and sensitivities to neurosteroids that may be exploited to increase our understanding of the way the brain functions and as potential sources of therapeutic action. Steroids such as progesterone, pregnenonlone and dehydropiandrosterone are normally associated with their peripheral origin and action but have recently been shown to be de-novo synthesized in the brain itself. Specifically, several reports have indicated the ability of neurosteroids to alter both inhibitory GABA) and excitatory NMDA) function. Determining selective and novel pathways to uor down regulate the excitability of the brain may reveal significant sources of new therapeutic potential.