Distinct bandwidths of orexin neuron activity independently encode body movement and metabolic state

Abstract

AbstractHypothalamic orexin/hypocretin neurons (HONs) are key orchestrators of metabolism and adaptive behaviors. HON activity varies rapidly across behavioral and metabolic states: active during periods of high arousal, and silent during quiescence. However, it is unknown whether HON activity tracks specific behaviors, or a general aspect of all behaviors, and whether this depends on metabolic state. After recording HON population dynamics in awake behaving mice, we performed a spectral analysis of HON encoding of spontaneous body movements and behaviors recorded via video-tracking. Multivariate analyses of distinct HON activity bandwidths revealed that movements were encoded at a higher frequency bandwidth than blood glucose, and imposing distinct metabolic states did not interfere with HON movement encoding. HON population activity tracked the total amount of body movement across multiple classified behaviors with a high degree of precision. At key projection targets, orexin/hypocretin peptide outputs correlated with self-initiated movement in a projection-specific manner, indicating functional heterogeneity in HON outputs. Finally, we found that body movement was not encoded to the same extent in other key neural clusters related to arousal or energy. Collectively, these data reveal a general principle behind HON activation in behaving animals, that is orthogonal to their reactions to metabolic shifts. This not only enhances our understanding of the fundamental roles of HONs in brain-body coordination, but also suggests novel non-invasive methods for monitoring HON population activity using video-tracked biometrics, which are pivotal for future investigations into how movement and energy demands are encoded by the brain.