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

J Antonio González, Panagiota Iordanidou, Molly Strom, Antoine Adamantidis, Denis Burdakov

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128 Citations (Scopus)
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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.

Original languageEnglish
Article number11395
Number of pages9
JournalNature Communications
Publication statusPublished - 22 Apr 2016

Bibliographical note

Acknowledgments: Work funded by a Marie Curie Intra-European Fellowship FP7-PEOPLE-2009-IEF Project number 255559 to J.A.G.). The authors declare no conflicts of interest.


  • Amygdala
  • Animals
  • Brain Mapping
  • Energy Metabolism
  • Exploratory Behavior
  • Fiber Optic Technology
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Hypothalamic Hormones
  • Hypothalamus
  • Male
  • Melanins
  • Mice
  • Mice, Transgenic
  • Neurons
  • Optogenetics
  • Orexin Receptors
  • Orexins
  • Patch-Clamp Techniques
  • Pituitary Hormones
  • Septal Nuclei
  • Stereotaxic Techniques
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Wakefulness
  • Journal Article
  • Research Support, Non-U.S. Gov't


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