Afferents to the Ventrolateral Preoptic Nucleus

TLDR

Sleep is regulated by circadian, affective, temperature, pain, and other factors, yet the neural pathways mediating these influences remain unknown. The study aims to identify pathways that may influence sleep by examining afferents to the ventrolateral preoptic nucleus (VLPO). The authors mapped afferents to the VLPO using retrograde and anterograde tracing and immunohistochemistry for monoaminergic markers. They found modest monoaminergic projections to the VLPO, dense histaminergic, noradrenergic, and serotonergic innervation, reciprocal connections with monoaminergic nuclei, and moderate to heavy inputs from hypothalamic, autonomic, limbic, and DMH regions, with sparse SCN, cholinergic, and dopaminergic inputs, indicating robust pathways linking arousal, autonomic, limbic, and circadian systems to sleep regulation.

Abstract

Sleep is influenced by diverse factors such as circadian time, affective states, ambient temperature, pain, etc., but pathways mediating these influences are unknown. To identify pathways that may influence sleep, we examined afferents to the ventrolateral preoptic nucleus (VLPO), an area critically implicated in promoting sleep. Injections of the retrograde tracer cholera toxin B subunit (CTB) into the VLPO produced modest numbers of CTB-labeled monoaminergic neurons in the tuberomammillary nucleus, raphe nuclei, and ventrolateral medulla, as well as a few neurons in the locus coeruleus. Immunohistochemistry for monoaminergic markers showed dense innervation of the VLPO by histaminergic, noradrenergic, and serotonergic fibers. Along with previous findings, these results suggest that the VLPO and monoaminergic nuclei may be reciprocally connected. Retrograde and anterograde tracing showed moderate or heavy inputs to the VLPO from hypothalamic regions including the median preoptic nucleus, lateral hypothalamic area, and dorsomedial hypothalamic nucleus (DMH), autonomic regions including the infralimbic cortex and parabrachial nucleus, and limbic regions including the lateral septal nucleus and ventral subiculum. Light to moderate inputs arose from orexin and melanin concentrating hormone neurons, but cholinergic or dopaminergic inputs were extremely sparse. Suprachiasmatic nucleus (SCN) projections to the VLPO were sparse, but the heavy input to the VLPO from the DMH, which receives direct and indirect SCN inputs, could provide an alternate pathway regulating the circadian timing of sleep. These robust pathways suggest candidate mechanisms by which sleep may be influenced by brain systems regulating arousal, autonomic, limbic, and circadian functions.