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

• Published in: Nature communications 2018-10, Vol.9 (1), p.4129-14, Article 4129
• Main Authors: Kroeger, Daniel, Absi, Gianna, Gagliardi, Celia, Bandaru, Sathyajit S., Madara, Joseph C., Ferrari, Loris L., Arrigoni, Elda, Münzberg, Heike, Scammell, Thomas E., Saper, Clifford B., Vetrivelan, Ramalingam
• Format: Article
• Language: English
• Subjects: 13/44; 13/51; 14/32; 14/34; 14/63; 38/1; 59; 631/378; 631/378/1385; 631/378/3920; 64; 64/110; Activation; Animals; Body temperature; Body Temperature Regulation - genetics; Body Temperature Regulation - physiology; Electroencephalography; Electromyography; Galanin; Galanin - genetics; Galanin - metabolism; Gene Expression Profiling; Heat loss; Humanities and Social Sciences; Insomnia; Latency; Lesions; Male; Mice; Mice, Transgenic; multidisciplinary; Neurons; Neurons - metabolism; Preoptic area; Preoptic Area - cytology; Preoptic Area - metabolism; Science; Science (multidisciplinary); Sleep; Sleep - genetics; Sleep - physiology; Sleep and wakefulness; Sleep disorders; Sleep Initiation and Maintenance Disorders - genetics; Sleep Initiation and Maintenance Disorders - metabolism; Sleep Initiation and Maintenance Disorders - physiopathology; Ventrolateral preoptic nucleus; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-06590-7

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 POA GAL neurons was shown to paradoxically cause waking, not sleep. Here we report that photostimulation of VLPO GAL 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 VLPO GAL neurons confirms the increase in sleep, and also reduces body temperature. In addition, chemogenetic activation of VLPO GAL neurons induces short-latency sleep in an animal model of insomnia. Collectively, these findings establish a causal role of VLPO GAL neurons in both sleep induction and heat loss. Anatomical lesions of the preoptic area (POA) can cause sleep loss while electrical, chemical, or thermal stimulation of POA can induce sleep. To better understand the exact neural function of the POA, this study shows that galanin and GABA+ inhibitory neurons in the ventrolateral POA that project to the wake-promoting tuberomammillary nucleus promote sleep in a stimulation frequency dependent manner.