My research interests focus on the role of specific melatonin receptors in setting the circadian rhythm of neuronal firing in the suprachiasmatic nucleus. We use the brain slice preparation and electrophysiological techniques to monitor neuronal firing over a circadian cycle. This work is possible because of the generation of strains of mice with specific genetic deletions of either the MT1 or/and MT2 melatonin receptors. We are developing strains of mice that will have each melatonin receptor fluorescently tagged, thus permitting patch clamp studies of a neuron endowed with a specific melatonin receptor.
Currently, the project seeks to identify environmental chemicals that differentially modulate melatonin receptor signaling in target tissues, which may disturb the intricate balance by MT1 and MT2 mediated processes leading to disruption of circadian rhythms and metabolic functions leading to increased risk of diabetes, obesity and metabolic disorders. We have identified the first examples (e.g., carbamate and pyrethroid insecticides, phthalates) of environmental melatonergic circadian disruptors (EMCD) targeting G protein-coupled melatonin receptors with in-vivo efficacy on circadian (chronobiological) behavioral responses in mice. Disruption of melatonin receptor signaling processes has the potential to disturb the rhythmic control and homeostasis of various circadian dependent physiological processes affecting behavioral, neurological, cognitive, and metabolic outputs modulated by brain (SCN) and peripheral clocks. The goal is to provide rational to further assess circadian rhythm risk factors to environmental chemical exposure and to develop guidelines and/or strategies for the use of selective interventions (e.g., light, melatonin) known to maintain circadian entrainment when delivered at the appropriate time.