Control Of Locomotor Speed,Arousal,and Hippocampal Theta Rhythms By The Nucleus Incertus

The ability to move through an environment to find food,social partners,habitats,or to avoid danger is fundamental for an animal's survival.When navigating at fast speed through a complex environment,an animal requires high arousal to sustain an attentive state and actively uses memory to update its awareness of environmental cues.However,the neural circuits for coordinately controlling these important processes remain to be fully dissected.Previous studies have hinted that the nucleus incertus(NI)—a brain region in the pontine brainstem—may be involved in some of these processes,although the underlying cell-type-specific circuit mechanisms have not been elucidated.In the present study,we want to examine(1)whether the neuronal activity in the NI is correlated with the locomotor speed,arousal,and hippocampal theta rhythms,(2)whether there is a causal role for NI neurons in controlling locomotion,arousal,and hippocampal theta rhythms,(3)how do NI neurons control locomotion,arousal,and hippocampal theta rhythms,and(4)if the NI truly participate in locomotor control,could we build a brain-to-brain interface(Bt BI)to transfer information at a sufficiently fast rate for real-time control of locomotion across individuals?We found that the activity of the neuromedin B(NMB)neurons in the 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 activation of NI NMB neurons.Their projections to multiple downstream stations differentially regulate locomotion,arousal and hippocampal theta,with the projection to the medial septum being particularly important for promoting arousal.Finally,we demonstrated an optical brain-to-brain interface that transmits information regarding locomotor speed from one mouse to another and allows precise,real-time control of locomotion across animals with information transfer rate about 2-3orders of magnitude higher than previous BtBIs.