Circadian rhythm disorders occur when the body's internal clock, located in the suprachiasmatic nucleus (SCN), is not properly synchronized (entrained) to the 24-hour solar day. Desynchronization of the circadian clock from the light-dark cycle can result in disturbed sleep, fatigue, and impaired performance characteristic of jet-lag and shift-work sleep disorder. In mammals, a subset of photosensitive retinal ganglion cells (RGCs) that contain the photopigment melanopsin transmits photic information to the SCN to entrain molecular, physiologic, and behavioral rhythms to the solar cycle. The inputs, projections, and neurotransmitters of RGCs that express melanopsin will be examined to better understand how light resets the circadian clock. Neuronal tracing and histochemical techniques will be used to determine whether these RGCs receive input from rods and cones, and whether these RGCs project to other brain regions involved in non-visual photic processing. The complement of neurotransmitters in RGCs that convey light as chemical signals will also be determined. Experimental findings will be used to construct a model that describes how light entrains the circadian clock to the solar day, and how uncoupling of the pacemaker from the light-dark cycle leads to circadian rhythm disorders. ? ?
Gooley, Joshua J; Schomer, Ashley; Saper, Clifford B (2006) The dorsomedial hypothalamic nucleus is critical for the expression of food-entrainable circadian rhythms. Nat Neurosci 9:398-407 |
Gooley, Joshua J; Lu, Jun; Fischer, Dietmar et al. (2003) A broad role for melanopsin in nonvisual photoreception. J Neurosci 23:7093-106 |