Galanin neurons in the ventrolateral preoptic area promote sleep and heat loss in mice

Abstract

The preoptic area (POA) is necessary for sleep, but the fundamental POA circuits have remained elusive. Previous studies showed that galanin (GAL)- and GABA-producing neurons in the ventrolateral preoptic nucleus (VLPO) express cFos after periods of increased sleep and innervate key wake-promoting regions. Although lesions in this region can produce insomnia, high frequency photostimulation of the POAGAL neurons was shown to paradoxically cause waking, not sleep. Here we report that photostimulation of VLPOGAL neurons in mice promotes sleep with low frequency stimulation (1–4 Hz), but causes conduction block and waking at frequencies above 8 Hz. Further, optogenetic inhibition reduces sleep. Chemogenetic activation of VLPOGAL neurons confirms the increase in sleep, and also reduces body temperature. In addition, chemogenetic activation of VLPOGAL neurons induces short-latency sleep in an animal model of insomnia. Collectively, these findings establish a causal role of VLPOGAL neurons in both sleep induction and heat loss.

Galanin neurons in the hypothalamus link sleep homeostasis, body temperature and actions of the α2 adrenergic agonist dexmedetomidine

“…On the other hand, optogenetic activation of PO galanin neuron soma produced wakefulness (64); this result could be caused by other galanin neuron subtypes (68). Our results on chronic lesioning, are consistent with others who found that acute chemogenetic and optogenetic activation of LPO galanin neurons induces induced both NREM sleep and hypothermia (49). Nevertheless, and even allowing for the high sleep-wake fragmentation that appears in LPO-DGal mice, we find that LPO galanin neurons are dispensable for achieving baseline NREM sleep.…”

“…Consistent with the above findings, chemogenetic activation of LPO Gal neurons with CNO in LPO-Gal-hM3Dq mice induced hypothermia ( Fig. S1A, B), as also reported by others (49). CNO had no measurable effect on baseline temperature in control mice ( Fig.…”

“…Chemogenetic activation of LPO Gal neurons with CNO in LPO-Gal-hM3Dq mice induced NREM sleep ( Fig. S3 A,B,C), as also reported by others (49). The power of this CNO-induced NREM sleep was higher than baseline power of NREM sleep after saline 8 injection ( Fig.…”

“…Nevertheless, and even allowing for the high sleep-wake fragmentation that appears in LPO-DGal mice, we find that LPO galanin neurons are dispensable for achieving baseline NREM sleep. But given that there are mixed populations of PO GABA (galanin and other peptide-expressing types) that induce NREM sleep (49,64); and that glutamate/NOS1 cells in MPO/MnPO can induce both NREM sleep and body cooling (31), perhaps this is not surprising Within the PO hypothalamic area, galanin-expressing neurons have quite different functions: galanin neurons coordinate parental behavior (motor, motivational, social) and mating (69,70), as well as temperature and sleep (49,56). We cannot rule out if one type of LPO galanin neuron increases NREM delta power, and another promotes chronic cooling.…”

Systemic serotonin inhibits brown adipose tissue sympathetic nerve activity via a GABA input to the dorsomedial hypothalamus, not via 5HT1A receptor activation in raphe pallidus

“…The source(s) of the relevant GABAergic inhibition to DMH neurones and the neural circuitry through which iv 5-HT activates this inhibition remain unknown. There is no shortage of potentially thermoregulatory-related GABAergic inputs to DMH, [21][22][23][61][62][63][64][65] any of which might be enhanced by iv 5-HT. Since systemically administered 5-HT could be transported across the blood brain barrier 17 or could act at circumventricular organs where there is an incomplete blood brain barrier, we cannot rule out a direct effect of iv 5-HT at 5-HTR within the central nervous system.…”