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

Daniel Kroeger,Clifford B Saper,Celia Gagliardi,Loris L Ferrari,Gianna Absi,Thomas E Scammell,Elda Arrigoni,Ramalingam Vetrivelan,Joseph C Madara,Sathyajit S Bandaru,Heike Münzberg

doi:10.1038/s41467-018-06590-7

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.

Highlights

The preoptic area (POA) is necessary for sleep, but the fundamental POA circuits have remained elusive
POAGAL neurons are predominantly found in three major clusters, including the ventrolateral preoptic nucleus (VLPO) and extended VLPO; the medial preoptic nucleus; and the supraoptic nucleus[11]
We found that in mice, a larger proportion of the VLPOGAL neurons is located in the dorsal extended VLPO

Summary

Introduction

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. Lesions in this region can produce insomnia, high frequency photostimulation of the POAGAL neurons was shown to paradoxically cause waking, not sleep. Many sleep-active VLPO neurons are activated by increased skin or body temperature (Tb), and may drive reductions in Tb, demonstrating the tight coupling of sleep and heat loss pathways[24,25] It is unknown whether VLPOGAL neurons contribute to thermoregulation. Chemoactivation of VLPOGAL neurons causes profound hypothermia, indicating that VLPOGAL neurons can promote heat loss

Methods

Results

Conclusion