Emerging concepts in baroreflex regulation of action potential subpopulations in human muscle sympathetic nerve activity

Baroreflex regulation of muscle sympathetic nerve activity (MSNA) represents a key mechanism defending blood pressure homeostasis. The original human microneurographic studies generated convincing evidence that the baroreflex strongly shapes MSNA into bursts and influences variations in burst frequency but weakly regulates burst amplitude. This review synthesizes these foundational integrated MSNA observations with emerging multi-unit action potential (AP) data to provide insight into baroreflex regulation of human sympathetic discharge during baseline and periods of physiological stress. The spontaneous baroreflex gain technique illustrates that differential baroreflex regulation of burst frequency versus amplitude stems from heterogeneous regulation over size-based AP subpopulations. During baseline, whereas medium APs that fire in most bursts exhibit strong baroreflex control, larger APs which predominantly fire in large bursts receive weak baro-regulation. During orthostasis, rises in MSNA are achieved by resetting the baroreflex operating point for medium APs upwards to greater firing probabilities and positions of stronger baroreflex control. Also, we have documented a subpopulation of asynchronous APs that are synchronized into bursts during orthostasis. During fatiguing handgrip exercise, interactions between central feed-forward and metaboreflex mechanisms ensure that the strength of AP baroreflex control is maintained but reset upwards to higher discharge and rightwards to greater pressures. Also, during orthostasis and fatiguing exercise, total MSNA is augmented by recruiting larger previously silent APs under weak baroreflex control. These observations suggest the existence of subpopulations of sympathetic neurons that receive heterogenous central baroreflex regulation. Transient AP baroreflex resetting may represent a strategy to support blood pressure homeostasis in humans.