Control of locomotor speed, arousal, and hippocampal theta rhythms by the nucleus incertus

Lihui Lu,Sice Wang,Rui Lin,Tao Yu,Jiawei Zeng,Lubin Tan,Zhixiang Liu,Yang Liu,Yuqi Ren,Minmin Luo,Qingchun Guo,Qiru Feng

doi:10.1038/s41467-019-14116-y

Abstract

Navigation requires not only the execution of locomotor programs but also high arousal and real-time retrieval of spatial memory that is often associated with hippocampal theta oscillations. However, the neural circuits for coordinately controlling these important processes remain to be fully dissected. Here we show that the activity of the neuromedin B (NMB) neurons in the nucleus incertus (NI) is tightly correlated with mouse locomotor speed, arousal level, and hippocampal theta power. These processes are reversibly suppressed by optogenetic inhibition and rapidly promoted by optogenetic stimulation of NI NMB neurons. These neurons form reciprocal connections with several subcortical areas associated with arousal, theta oscillation, and premotor processing. Their projections to multiple downstream stations regulate locomotion and hippocampal theta, with the projection to the medial septum being particularly important for promoting arousal. Therefore, NI NMB neurons functionally impact the neural circuit for navigation control according to particular brains states.

Highlights

Navigation requires the execution of locomotor programs and high arousal and real-time retrieval of spatial memory that is often associated with hippocampal theta oscillations
We initially found that nucleus incertus (NI) neuromedin B (NMB) neuronal activity is significantly correlated with locomotor speed, arousal levels, and hippocampal theta power
Taking advantage of the previous finding that within the brainstem the neuromedin B (NMB) gene is preferentially expressed in the NI19, we used the CRISPR-Cas[9] method to generate a knockin mouse line (NMB-Cre), in which the Cre recombinase is expressed under the control of the NMB promoter (Supplementary Fig. 1a)

Summary

Introduction

Navigation requires the execution of locomotor programs and high arousal and real-time retrieval of spatial memory that is often associated with hippocampal theta oscillations. We show that the activity of the neuromedin B (NMB) neurons in the nucleus incertus (NI) is tightly correlated with mouse locomotor speed, arousal level, and hippocampal theta power. These processes are reversibly suppressed by optogenetic inhibition and rapidly promoted by optogenetic stimulation of NI NMB neurons. Circuit mapping and electrophysiological recordings showed that NI NMB neurons integrate information associated with arousal and locomotor activity; they send out both GABAergic and glutamatergic projections to a number of brain areas associated with locomotion, arousal, and theta rhythms. Projection-specific inhibition demonstrated that the control of arousal by NI NMB neurons requires predominantly the projection to the medial septum and that the control of locomotion and hippocampal theta likely requires the coordinated activity of multiple downstream projections

Methods

Results

Conclusion