Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks.
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.
The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
J Antonio
JA
González
The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.
Panagiota
P
Iordanidou
MRC NIMR, London NW7 1AA, UK.|Sainsbury Wellcome Centre, UCL, London W1T 4JG, UK.
Molly
M
Strom
Department of Neurology, University of Bern, Bern University Hospital, 3010 Bern, Switzerland.
Antoine
A
Adamantidis
The Francis Crick Institute, Mill Hill Laboratory, London NW7 1AA, UK.|Department of Developmental Neurobiology, King's College London, London WC2R 2LS, UK.
Denis
D
Burdakov
D000679:Amygdala / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001931:Brain Mapping; D004734:Energy Metabolism / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology; D005336:Fiber Optic Technology; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D007028:Hypothalamic Hormones / Q000235:genetics / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008543:Melanins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D062308:Optogenetics; D064446:Orexin Receptors / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010907:Pituitary Hormones / Q000235:genetics / Q000378:metabolism*; D012686:Septal Nuclei / Q000166:cytology / Q000378:metabolism; D013238:Stereotaxic Techniques; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D014851:Wakefulness / Q000235:genetics
C000596233:Hcrt protein, mouse; C497459:Hcrtr1 protein, mouse; D007028:Hypothalamic Hormones; D008543:Melanins; D064446:Orexin Receptors; D000068797:Orexins; D010907:Pituitary Hormones; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; C019463:melanin-concentrating hormone