| The suprachiasmatic nucleus (SCN), a small paired structure in the hypothalamus of the mammalian brain, regulates the daily rhythmicity of many physiological and biological variables, including sleep-wake behavior. The ventrolateral preoptic nucleus (VLPO), a bilateral cell group located in the nearby preoptic area, is implicated in sleep regulation. Efferent connections from the SCN may directly or indirectly regulate the circadian timing of sleep at the level of the VLPO; the presence of these fibers were investigated in rats using neuroanatomic tracing techniques. To define the borders of the VLPO and to distinguish a convenient cytoplasmic marker for VLPO cells, sleep-active cells were shown to express the neurotransmitter galanin via double-label immunohistochemical and in situ hybridization techniques in tissue from polysomnographically-recorded sleeping rats; these cells reached beyond the originally-described borders of the VLPO into the medial and dorsal “extended VLPO.” Similar techniques were also used to find and localize the VLPO in mice, degus, and cats; the presence of galanin mRNA was also used to identify the VLPO in monkeys and humans, demonstrating that this cell group is a common feature of mammalian brains. Interestingly, the volume of this galaninergic nucleus shrinks with age in humans, perhaps accounting for sleep deficits in elderly people.; To demonstrate direct connections from the SCN to the VLPO in rats, injections of anterograde tracer were stereotaxically placed into the SCN, and tissue was immunohistochemically processed. Staining revealed a modest number of direct efferents from the SCN to the galaninergic VLPO, including to the medial extended VLPO. Additional neuroanatomic pathways from the SCN to the VLPO were revealed by investigating possible disynaptic routes. Retrograde and anterograde tracers were simultaneously placed into the VLPO and SCN, respectively. Anterogradely-labeled fibers from the SCN apposed retrogradely-labeled cell bodies that project to the VLPO in several regions, most intensely in the dorsomedial hypothalamic nucleus (DMH). Experimental evidence also supported a trisynaptic amplification of the SCN's output to the DMH via the subparaventricular zone (SPZ). Thus, SCN → DMH → VLPO and SCN → SPZ → DMH → VLPO routes may provide biologically-important pathways for the circadian regulation of sleep. |
