Glycine receptors in the central nervous system
One of my laboratory’s interests is the cortical inhibitory glycine receptor (GlyR) and the other is the ketogenic diet. Both projects share the goal of developing novel therapies for those with medically resistant epilepsy.
GlyRs are expressed throughout the central nervous system, but their function is known only in the brainstem and spinal cord where they participate in fast inhibitory neurotransmission. Their function in the cortex is less clear, though in mature vertebrates they are inhibitory like gamma-aminobutyric acid A receptors (GABARs). This property raises the possibility that GlyR modulators may be as useful as GABAR modulators in treating epilepsy and other neuropsychiatric disorders. However, GlyRs have not been exploited as a therapeutic target to the extent that GABAARs have. Therefore, we have been interested in determining the physiological role of GlyRs in the forebrain and to determine how they are modulated. We have been using patch clamp electrophysiology to study GlyRs in cultured embryonic mouse hippocampal neurons and in mouse hippocampal slices to accomplish these goals.
The ketogenic diet is a high fat, adequate protein and low carbohydrate diet used to treat children and adults whose epilepsy does not respond to medication. Despite its effectiveness, the diet is not an option for all with medically resistant epilepsy because it is difficult to implement and maintain and because it has side effects. For these reasons, understanding how it dampens neuronal excitability is potentially useful. Specifically, we have been testing the hypothesis that the hormone leptin mediates some of its anticonvulsant effects. We have been using leptin deficient (ob/ob) mice, leptin receptor deficient (db/db) mice, and green fluorescent protein (GFP) expressing mice combined with both in vitro and in vivo electrophysiology and confocal microscopy to test this hypothesis.