Subregional organization of preoptic area/anterior hypothalamic projections to arousal-related monoaminergic cell groups

Pathways mediating the generation and/or maintenance of sleep reside within the preoptic/ anterior hypothalamus (POAH). Reproduction, water balance, t hermoregulation, and neuroendocrine functions are also associated with POAH , but it is not fully understood whether sleep is consolidated with these b ehavioral and physiological functions, or whether sleep-related circuitry i s segregated from other POAH regions. Recent studies indicate that sleep me chanisms may be localized to the ventrolateral preoptic area (VLPO) and tha t this region sends inhibitory projections to walking/arousal-related neuro ns in the histaminergic tuberomammillary nucleus (TM), the noradrenergic lo cus coeruleus (LC), and the serotonergic dorsal raphe (DR). The present stu dy is a quantitative investigation of preoptic area efferents to these mono aminergic groups. The results demonstrate that biotinylated dextran injecti ons in the VLPO region reveal a robust innervation of TM that was as much a s five times greater than innervation derived from other POAH subregions. T he innervation of TM originated almost exclusively from injection sites in the region of galanin neurons. VLPO projections to the LC were moderately d ense and were greater than in other POAH regions except for equivalent inpu t from the medial preoptic area. Projections to the dorsal raphe were equiv alent to LC innervation and were generally two to three times greater from VLPO than from other POAH regions, except for projections from the lateral preoptic region, which were similar in magnitude. The rostral and caudal le vels projected more to the TM, whereas the midrostral region of VLPO strong ly innervated the LC core. These findings, with recent studies demonstratin g medial and lateral extensions of the sleep-related VLPO neuronal group, i ndicate that descending arousal state control may be mediated by this speci fic galaninergic/gamma -aminobutyric acid (GABA)ergic cell group. J. Comp. Neural. 429:638-653, 2001. (C) 2001 Wiley-Liss, Inc.