Differential Control of Muscle Sympathetic Single-Unit Activity in Humans


Background: The sympathetic nervous system plays a critical role in blood pressure regulation at rest and during stress. Sympathetic neural activity directed towards skeletal muscle constricts the vasculature to raise resistance within the arterial tree. Interestingly, within a bundle of muscle sympathetic nerves, despite being directed towards the same skeletal muscle vascular targets, the regulation of each fibre can be different in response to the same stress. Largely unknown are the control systems underpinning this level of differential control. Purpose: The present thesis aimed at quantifying differential control patterns of individual muscle sympathetic fibres in response to different physiological stressors in young healthy humans. Methods: Muscle sympathetic nerve activity was recorded using microelectrode placement into the fibular nerve (microneurography). Tracking the activity of individual muscle sympathetic fibres within the nerve bundle was achieved using action potential amplitude and waveform matching techniques. Results: We observed individual muscle sympathetic single units to be either activated, non- responsive, or inhibited, during cardiopulmonary baroreceptor unloading (non-hypotensive lower body negative pressure), arterial baroreceptor unloading and loading (sequential bolus injections of a vasodilator and vasoconstrictor agent, respectively), rhythmic handgrip exercise, and isolated muscle metaboreflex activation (post-exercise circulatory occlusion after a static handgrip contraction). We demonstrate that single units do not have fixed response patterns but rather their directionality of response are dependent on the level of sympathoexcitation. Conclusions: The findings of this thesis establish differential control as a normal phenomenon of sympathetic regulation, which is likely mediated by different response thresholds within central autonomic circuitry and the result of summation of multiple neural inputs. Thus, individual postganglionic fibres can engage in multiple response patterns dependent on the milieu of summated neural inputs within the brainstem and the weighted influence of these neural inputs on the activity of each single unit.