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

Nat Commun. 2016 Apr 22;7:11395. doi: 10.1038/ncomms11395.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / cytology
  • Amygdala / metabolism
  • Animals
  • Brain Mapping
  • Energy Metabolism / genetics
  • Exploratory Behavior / physiology
  • Fiber Optic Technology
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Hypothalamic Hormones / genetics
  • Hypothalamic Hormones / metabolism*
  • Hypothalamus / cytology
  • Hypothalamus / metabolism*
  • Male
  • Melanins / genetics
  • Melanins / metabolism*
  • Mice
  • Mice, Transgenic
  • Neurons / classification
  • Neurons / cytology
  • Neurons / metabolism*
  • Optogenetics
  • Orexin Receptors / genetics
  • Orexin Receptors / metabolism*
  • Orexins / genetics
  • Orexins / metabolism*
  • Patch-Clamp Techniques
  • Pituitary Hormones / genetics
  • Pituitary Hormones / metabolism*
  • Septal Nuclei / cytology
  • Septal Nuclei / metabolism
  • Stereotaxic Techniques
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Wakefulness / genetics

Substances

  • Hcrt protein, mouse
  • Hcrtr1 protein, mouse
  • Hypothalamic Hormones
  • Melanins
  • Orexin Receptors
  • Orexins
  • Pituitary Hormones
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • melanin-concentrating hormone