Control of Emotion and Wakefulness by Neurotensinergic Neurons in the Parabrachial Nucleus

 Jingwen Chen1,2 · Noam Gannot2,3 · Xingyu Li2  · Rongrong Zhu1  · Chao Zhang1  · Peng Li2,3,4
1 Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 201619, China
2 Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
3 Department of Biologic and Materials Sciences, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA
4 Department of Molecular and Integrative Physiology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, USA

Abstract
The parabrachial nucleus (PBN) integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing, emotion, and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem. However, the precise identity and function of distinct PBN subpopulations are still largely unknown. Here, we leveraged molecular characterization, retrograde tracing, optogenetics, chemogenetics, and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain, rather than the medulla. Their activation induces freezing and anxiety-like behaviors, which in turn result in tachypnea. In addition, optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture. We propose that these neurons comprise a PBN subpopulation with specific gene expression, connectivity, and function, which play essential roles in behavioral and physiological regulation.

Keywords
Parabrachial nucleus; Neurotensin; Anxiety; Sleep; Wakefulness; Breathing; Neural circuit; Freezing; Medulla