Median Preoptic Nucleus and the Control of Sleep

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A role for the preoptic area (POA) of the hypothalamus in the control of sleep is supported by the results of lesion, stimulation and neuronal recording experiments. The precise location of putative sleep-regulatory cell groups within the POA is incompletely understood, but recent progress has been made through application of the c-fos protein immunoreactivity (IR) method. A localized group of neurons in the ventrolateral POA (vlPOA) that exhibit Fos-IR during sleep has been described in rat. vlPOA neurons have been shown to project to monoaminergic arousal systems in the posterior hypothalamus and brainstem and to contain the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Neuronal recording studies confirmed the presence of neurons with sleep-related discharge patterns within the vlPOA. The goal of proposed work is to characterize the anatomy and physiology of a second POA region where neurons exhibiting seep- related Fos-IR have been localized, the median preoptic nucleus (MnPN). Proposed experiments will answer the following questions: 1) Does the MnPN contain a high concentration of neurons with sleep-related discharge patterns, like that previously found in the vlPOA? 2) Are MnPN neurons that exhibit sleep-related Fos-IR also GABAergic? 3) Do MnPN neurons that exhibit sleep-related Fos-IR project to arousal systems in the magnocellular basal forebrain, the perifornical region of the lateral hypothalamus, the dorsal raphe nucleus and the dorsolateral pons? 4) Are a subset of MnPN neurons with sleep- related discharge also thermosensitive, as has been previously shown for vlPOA neurons? 5) Are MnPN neurons that are involved in the control of body fluid homeostasis a separate population from sleep-related MnPN neurons? Proposed work will examine in depth the anatomical, neurochemical, and electrophysiological features of an important POA neuronal group, the MnPN. Planned experiments will contribute to a more complete understanding of the role of hypothalamic mechanisms in normal and disordered sleep and arousal states.