Dissecting Neural Circuits for Top-Down Control of Sympathetic Functions

/Project Summary As an essential component of most behaviors, the sympathetic system regulates many vital physiological processes, such as heart rate, blood pressure, and respiration. Sympathetic activities exhibit an arousal state- dependent basal level (tone), which is subject to behavioral context-dependent regulation (activation and inactivation). In contrast to its importance, much less is known about top-down sympathetic regulation. Our recent studies reveal several populations of spinal projecting neurons (SPNs) with the capacity to regulate sympathetic preganglionic neurons. We hypothesize that medullary and hypothalamic SPNs may form parallel circuits to control state-dependent sympathetic activities with or without accompanying motor engagement. The objective of this proposed study is to test this hypothesis by analyzing the fundamental circuit architectures of sympathetic controlling SPNs, and determining the roles of these SPNs in regulating the basal tone of sympathetic activity, as well as their response to exercise and pain. The outcomes of this study are expected to advance the fundamental knowledge about autonomic regulation and its health impact. Project Number: 1R01NS142815-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: ZHIGANG HE (+1 co-PI) | Institution: BOSTON CHILDREN'S HOSPITAL, BOSTON, MA | Award Amount: $674,950 | Activity Code: R01 | Study Section: Sensory-Motor Neuroscience Study Section[SMN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11295258