UCLA

The temporal patterning of biological function is regulated by the circadian system on the cellular and systemic levels. In mammals, rhythmic neural output from the suprachiasmatic nucleus (SCN) of the hypothalamus provides the temporal cues needed to sustain synchronous cellular oscillations within tissues throughout the body, and coordinate those rhythms across systems to generate patterns of behavior and physiology essential for health and well-being. Genetic factors that may contribute to the dysfunction of the circadian system include sex, alterations in vasoactive intestinal peptide (VIP) signaling, and the Huntington’s disease (HD) causing mutation, all of which are associated with the increased prevalence of behavioral and physiological rhythm disruptions. By examining the SCN for patterns of electrical activity and alteration in the ionic mechanisms that regulate those activities, we determined sex differences in the balance between GABA excitation and inhibition may predispose females to circadian disruption. Secondly, disrupted electrical activity rhythms in animals lacking VIP is associated with deficits in rhythmic behavior/physiology and photic entrainment. Thirdly, reduced A-type/H and enhanced BK potassium currents are associated with the loss of rhythmic SCN electrical activity in the BACHD mouse model of HD.