The Stocker laboratory explores how the central nervous system senses neurohumoral signals to regulate body fluid homeostasis (water and salt balance) and cardiovascular function. These sensory signals arise from the circulation or cerebrospinal fluid as well as local environments such as the kidney. Unique sensory neurons transmit such information to integration centers within the hypothalamus to coordinate changes in behavior (thirst and salt appetite), neuroendocrine function (anti-diuretic hormone or vasopressin), and the activity of the autonomic nervous system. Alterations in sensory function, integration of these signals, or coordinated responses commonly contributes to cardiovascular disease including hypertension. To address these questions, the laboratory uses a number of approaches including in vivo neurophysiology, in vitro electrophysiology, opto- and chemo-genetic tools, in vivo cardiovascular monitoring, and translational studies in humans.
Project 1 investigates how dietary salt intake contributes to cardiovascular disease. Compelling evidence indicates that dietary salt acts centrally with other factors (genetic, hormonal) to elevate sympathetic nerve activity, blood pressure variability, and blood pressure. Time-controlled studies in both humans and animals indicate dietary salt intake elevates plasma or cerebrospinal fluid Na+ concentrations. A major goal of our laboratory is to identify the cellular mechanisms that permit specialized “Na+-sensing neurons” or osmoreceptors in the hypothalamus to sense changes in Na+ and lead to cardiovascular disease.
Project 2 explores how changes in the kidney activate renal sensory nerves to alter cardiovascular function. Multiple clinical trials have demonstrated renal denervation lowers blood pressure in humans and multiple experimental models in the laboratory. We are using a multi-faceted approach to understand what the renal sensory nerves detect, the central anatomical circuitry, and mechanisms by which such sensory nerves alter cardiovascular function.
Ong J, Kinsman BJ, Sved AF, Rush BM, Tan RJ, Carattino MD, Stocker SD. Renal Sensory Nerves Increase Sympathetic Nerve Activity and Blood Pressurein 2-Kidney 1-Clip Hypertensive Mice. Journal of Neurophysiology. PMID 31091159 DOI: 10.1152/jn.00173.2019
Stocker SD, Sved AF, Andresen MC. Missing Pieces of the Piezo1/Piezo2 Baroreceptor Hypothesis: An Autonomic Perspective. Journal of Neurophysiology. PMID 31314636 DOI: 10.1152/jn.00315.2019
Kinsman BJ, Simmonds SS, Browning KN, Wenner MM, Farquhar WB, Stocker SD. Integration of Hypernatremia and Angiotensin II by the Organum Vasculosum of the Lamina Terminalis Regulates Thirst. The Journal of Neuroscience : the Official Journal of the Society For Neuroscience. PMID 32005766 DOI: 10.1523/JNEUROSCI.2208-19.2020
Kinsman BJ, Simmonds SS, Browning KN, STOCKER SD. Organum vasculosum of the lamina terminalis detects NaCl to elevate sympathetic nerve activity and blood pressure. Hypertension69: 163-170, 2017.
Kinsman BJ, Browning KN, STOCKER SD. NaCl and osmolarity produce different responses in organum vasculosum of the lamina terminalis neurons, sympathetic nerve activity and blood pressure. J Physiol595: 6187-6201, 2017.
Nation H, Nicoleau M, Kinsman BJ, Browning KN, STOCKER SD. DREADD-induced activation of subfornical organ neurons stimulates thirst and salt appetite. J Neurophysiol115: 3123-3129, 2016.
STOCKER SD, Lang SM, Simmonds SS, Wenner ME, Farquhar WB. Cerebrospinal fluid hypernatremia elevates sympathetic nerve activity and blood pressure via rostral ventrolateral medulla. Hypertension 66: 1184-1190, 2015.