A neural basis for antagonistic control of feeding and compulsive behaviors

Leandra R Mangieri,Yungang Lu,Ryan M Cassidy,Qingchun Tong,Yong Xu,Benjamin R Arenkiel,Yuanzhong Xu

doi:10.1038/s41467-017-02534-9

Abstract

Abnormal feeding often co-exists with compulsive behaviors, but the underlying neural basis remains unknown. Excessive self-grooming in rodents is associated with compulsivity. Here, we show that optogenetically manipulating the activity of lateral hypothalamus (LH) projections targeting the paraventricular hypothalamus (PVH) differentially promotes either feeding or repetitive self-grooming. Whereas selective activation of GABAergic LH→PVH inputs induces feeding, activation of glutamatergic inputs promotes self-grooming. Strikingly, targeted stimulation of GABAergic LH→PVH leads to rapid and reversible transitions to feeding from induced intense self-grooming, while activating glutamatergic LH→PVH or PVH neurons causes rapid and reversible transitions to self-grooming from voracious feeding induced by fasting. Further, specific inhibition of either LH→PVH GABAergic action or PVH neurons reduces self-grooming induced by stress. Thus, we have uncovered a parallel LH→PVH projection circuit for antagonistic control of feeding and self-grooming through dynamic modulation of PVH neuron activity, revealing a common neural pathway that underlies feeding and compulsive behaviors.

Highlights

Abnormal feeding often co-exists with compulsive behaviors, but the underlying neural basis remains unknown
Cre is abundantly expressed in the lateral hypothalamus (LH), the dorsal medial hypothalamus (DMH), the Arc, and preoptic areas, but not in the PVH21
Our results showed that parallel GABAergic and glutamatergic LH→paraventricular hypothalamus (PVH) projections can differentially promote feeding vs. repetitive selfgrooming by modulating PVH neuron activity

Summary

Introduction

Abnormal feeding often co-exists with compulsive behaviors, but the underlying neural basis remains unknown. Excessive self-grooming in rodents is associated with compulsivity. We show that optogenetically manipulating the activity of lateral hypothalamus (LH) projections targeting the paraventricular hypothalamus (PVH) differentially promotes either feeding or repetitive self-grooming. Whereas selective activation of GABAergic LH→PVH inputs induces feeding, activation of glutamatergic inputs promotes self-grooming. Specific inhibition of either LH→PVH GABAergic action or PVH neurons reduces self-grooming induced by stress. We have uncovered a parallel LH→PVH projection circuit for antagonistic control of feeding and self-grooming through dynamic modulation of PVH neuron activity, revealing a common neural pathway that underlies feeding and compulsive behaviors. It has been suggested that compulsive behaviors associated with anorexia nervosa may manifest as a way to relieve stress and anxiety. Current studies demonstrate that the LH contains two distinct groups of neurons that exert opposite actions on feeding regulation

Methods

Results

Conclusion