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

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

Research output: Contribution to journalArticle

56 Citations (Scopus)
3 Downloads (Pure)

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.

Original languageEnglish
Article number11395
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 22 Apr 2016

Fingerprint

melanin
hormones
concentrating
brain
Brain
hypothalamus
Lateral Hypothalamic Area
neurons
Neurons
cells
wakefulness
Septal Nuclei
melanin-concentrating hormone
Wakefulness
Amygdala
Energy balance
Reward
deactivation
stimuli
Energy Metabolism

Keywords

  • 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

Cite this

Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks. / González, J Antonio; Iordanidou, Panagiota; Strom, Molly; Adamantidis, Antoine; Burdakov, Denis.

In: Nature Communications, Vol. 7, 11395, 22.04.2016.

Research output: Contribution to journalArticle

González, J Antonio ; Iordanidou, Panagiota ; Strom, Molly ; Adamantidis, Antoine ; Burdakov, Denis. / Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks. In: Nature Communications. 2016 ; Vol. 7.
@article{501210af5eec43f5ac104de1bcf6635b,
title = "Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks",
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.",
keywords = "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",
author = "Gonz{\'a}lez, {J Antonio} and Panagiota Iordanidou and Molly Strom and Antoine Adamantidis and Denis Burdakov",
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.",
year = "2016",
month = "4",
day = "22",
doi = "10.1038/ncomms11395",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks

AU - González, J Antonio

AU - Iordanidou, Panagiota

AU - Strom, Molly

AU - Adamantidis, Antoine

AU - Burdakov, Denis

N1 - 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.

PY - 2016/4/22

Y1 - 2016/4/22

N2 - 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.

AB - 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.

KW - Amygdala

KW - Animals

KW - Brain Mapping

KW - Energy Metabolism

KW - Exploratory Behavior

KW - Fiber Optic Technology

KW - Gene Expression Regulation

KW - Gene Regulatory Networks

KW - Hypothalamic Hormones

KW - Hypothalamus

KW - Male

KW - Melanins

KW - Mice

KW - Mice, Transgenic

KW - Neurons

KW - Optogenetics

KW - Orexin Receptors

KW - Orexins

KW - Patch-Clamp Techniques

KW - Pituitary Hormones

KW - Septal Nuclei

KW - Stereotaxic Techniques

KW - Vesicular Inhibitory Amino Acid Transport Proteins

KW - Wakefulness

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ncomms11395

DO - 10.1038/ncomms11395

M3 - Article

C2 - 27102565

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 11395

ER -