The long term goal of this research is to provide an understanding of the complex neural substrate underlying the organization of circadian rhythms.
The specific aims of this proposal are directed toward the common goal of furnishing a detailed analysis of the neural pathways linking the retina, the hypothalamic suprachiasmatic nucleus (SCN) and the thalamic intergeniculate leaflet (IGL). Increased knowledge of the neural pathways participating in the regulation of hypothalamic function is central to the amelioration of many human health problems. An understanding of circadian organization is relevant to problems of sleep, jet lag and some kinds of serious affective disorders. Using neuroanatomical techniques, the nature of the retinal input to the hypothalamus will be described in detail. The morphological characteristics of retinal ganglion cells afferent to: 1) the SCN; 2) the hypothalamic paraventricular nucleus (PVN); and 3) both the SCN and IGL will be determined by first identifying the central targets of these cells using intracerebrally injected fluorescent tracers. Dendrites of retrogradely labeled cells are then filled by intracellular dye injection. Using new tracing techniques, the retinohypothalamic tract in the human brain will be described in this proposal. Other morphological experiments at the light and electron microscopic level will examine the visual pathways of the subterranean mole rat, an animal which may have lost through evolution all but the retinohypothalamic tract. The synaptic organization of retinal inputs to the IGL will be studied using tracing techniques combined with immunocytochemistry at the ultrastructural level of analysis. A single behavioral experiment will explore the functional role of the IGL in mediating photic signals underlying the entrainment of circadian rhythms to environmental light:dark cycles.
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