Excessive food intake and peripheral infectious challenge are associated with increases in non-rapid eye movement sleep (NREMS). The vagus and vagal-induced upregulation of cytokines seems to mediate these sleep responses, in part. However, whether action potentials in the vagus induce cytokine upregulation in the brain and the central circuit tying vagal afferents to increased sleep and cytokine production remains unknown. Vagal-mediated intracerebral increases in cytokine mRNA levels have been observed in the brainstem and hypothalamus, two areas implicated in regulating NREMS. Neuroanatomical localization of the cell types involved in these increased cytokine mRNA levels are evaluated in a series of experimental tests. The following hypotheses are evaluated: (1) action potentials in vagal afferents are responsible and (2) the neural circuitry from the vagal afferent projection to the nucleus of the solitary tract through the lateral parabrachial nucleus to the anterior hypothalamus and medial preoptic area is responsible. Finally, the hypotheses that neurons within this circuitry are upregulating their cytokine mRNA levels in a vagal-mediated fashion is tested by retrogradely labeling specific neural projections. Mapping the vagal-mediated intracerebral cytokines within the brainstem and hypothalamus will provide new insights into the functional neuroanatomy that underlies the regulation of NREMS.
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