Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks

• Published in: Nature communications Vol. 7; no. 1; p. 11395
• Main Authors: González, J. Antonio, Iordanidou, Panagiota, Strom, Molly, Adamantidis, Antoine, Burdakov, Denis
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-04-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/34; 631/378/1385; 631/378/3920; 631/45/776/1178; 631/45/882; 9/74; Amygdala - cytology; Amygdala - metabolism; Animals; Brain Mapping; Energy; Energy Metabolism - genetics; Exploratory Behavior - physiology; Fiber Optic Technology; Gene Expression Regulation; Gene Regulatory Networks; Humanities and Social Sciences; Hypothalamic Hormones - genetics; Hypothalamic Hormones - metabolism; Hypothalamus; Hypothalamus - cytology; Hypothalamus - metabolism; Male; Melanins - genetics; Melanins - metabolism; Mice; Mice, Transgenic; multidisciplinary; Neurons; Neurons - classification; Neurons - cytology; Neurons - metabolism; Neurosciences; Optogenetics; Orexin Receptors - genetics; Orexin Receptors - metabolism; Orexins - genetics; Orexins - metabolism; Patch-Clamp Techniques; Pituitary Hormones - genetics; Pituitary Hormones - metabolism; Science; Science (multidisciplinary); Sensory perception; Septal Nuclei - cytology; Septal Nuclei - metabolism; Stereotaxic Techniques; Vesicular Inhibitory Amino Acid Transport Proteins; Wakefulness - genetics; United Kingdom > UK
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11395

The lateral hypothalamus (LH) controls energy balance. LH melanin-concentrating-hormone (MCH) and orexin/hypocretin (OH) neurons mediate energy accumulation and expenditure, respectively. MCH cells promote memory and appropriate stimulus-reward associations; their inactivation disrupts energy-optimal behaviour and causes weight loss. However, MCH cell dynamics during wakefulness are unknown, leaving it unclear if they differentially participate in brain activity during sensory processing. By fiberoptic recordings from molecularly defined populations of LH neurons in awake freely moving mice, we show that MCH neurons generate conditional population bursts. This MCH cell activity correlates with novelty exploration, is inhibited by stress and is inversely predicted by OH cell activity. Furthermore, we obtain brain-wide maps of monosynaptic inputs to MCH and OH cells, and demonstrate optogenetically that VGAT neurons in the amygdala and bed nucleus of stria terminalis inhibit MCH cells. These data reveal cell-type-specific LH dynamics during sensory integration, and identify direct neural controllers of MCH neurons.
Hypothalamic neurons expressing melanin-concentrating-hormone (MCH) maintain body weight by orchestrating behaviour and metabolism, but little is known about their intrinsic regulation. Here, Gonzalez and colleagues reveal their behaviour-related dynamics during wakefulness, and map their brain-wide neural inputs.