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

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

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.

Highlights

The lateral hypothalamus (LH) controls energy balance
The present study aims to address this missing information about LH neurons, by exploring (i) how MCH and OH population dynamics evolve in real-time during sensory experiences in awake mice; (ii) what brain centres directly innervate MCH and OH neurons and (iii) how genetically and anatomically defined input circuits shape MCH neuron activity
We find differential modulation of MCH and OH cell activity during wakefulness, and show that MCH and OH cells receive direct neural inputs from multiple brain areas, including inhibitory inputs to MCH cells from the amygdala and bed nucleus of stria terminalis

Summary

Introduction

The lateral hypothalamus (LH) controls energy balance. LH melanin-concentrating-hormone (MCH) and orexin/hypocretin (OH) neurons mediate energy accumulation and expenditure, respectively. 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. 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. We find differential modulation of MCH and OH cell activity during wakefulness, and show that MCH and OH cells receive direct neural inputs from multiple brain areas, including inhibitory inputs to MCH cells from the amygdala and bed nucleus of stria terminalis

Methods

Results

Conclusion