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

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

doi:10.1038/ncomms11395

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

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

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

126 Citations (Scopus)

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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 language	English
Article number	11395
Number of pages	9
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11395
Publication status	Published - 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.

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

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Awake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks
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Final published version, 2.17 MBLicence: CC BY

Antonio Gonzalez
- School of Medicine, Medical Sciences & Nutrition, The Rowett Institute of Nutrition and Health - Lecturer
- School of Medicine, Medical Sciences & Nutrition, Aberdeen Cardiovascular and Diabetes Centre
Person: Academic

Cite this

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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. ",

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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.",

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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.

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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.

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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

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KW - Mice, Transgenic

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KW - Patch-Clamp Techniques

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KW - Stereotaxic Techniques

KW - Vesicular Inhibitory Amino Acid Transport Proteins

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KW - Journal Article

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SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 11395

ER -

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

Abstract

Bibliographical note

Keywords

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Antonio Gonzalez

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