Modulation of Human Muscle Spindle Discharge by Arterial Pulsations - Functional Effects and Consequences Ingvars Birznieks1,2,5*, Tjeerd W. Boonstra3,6, Vaughan G. Macefield2,4 1 School of Science and Health, University of Western Sydney, Sydney, New South Wales, Australia, 2 Neuroscience Research Australia, Sydney, New South Wales, Australia, 3 Black Dog Institute, Sydney, New South Wales, Australia, 4 School of Medicine, University of Western Sydney, Sydney, New South Wales, Australia, 5 School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia, 6 School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia Abstract Arterial pulsations are known to modulate muscle spindle firing; however, the physiological significance of such synchronised modulation has not been investigated. Unitary recordings were made from 75 human muscle spindle afferents innervating the pretibial muscles. The modulation of muscle spindle discharge by arterial pulsations was evaluated by R-wave triggered averaging and power spectral analysis. We describe various effects arterial pulsations may have on muscle spindle afferent discharge. Afferents could be ‘‘driven’’ by arterial pulsations, e.g., showing no other spontaneous activity than spikes generated with cardiac rhythmicity. Among afferents showing ongoing discharge that was not primarily related to cardiac rhythmicity we illustrate several mechanisms by which individual spikes may become phase-locked. However, in the majority of afferents the discharge rate was modulated by the pulse wave without spikes being phase locked. Then we assessed whether these influences changed in two physiological conditions in which a sustained increase in muscle sympathetic nerve activity was observed without activation of fusimotor neurones: a maximal inspiratory breath- hold, which causes a fall in systolic pressure, and acute muscle pain, which causes an increase in systolic pressure. The majority of primary muscle spindle afferents displayed pulse-wave modulation, but neither apnoea nor pain had any significant effect on the strength of this modulation, suggesting that the physiological noise injected by the arterial pulsations is robust and relatively insensitive to fluctuations in blood pressure. Within the afferent population there was a similar number of muscle spindles that were inhibited and that were excited by the arterial pulse wave, indicating that after signal integration at the population level, arterial pulsations of opposite polarity would cancel each other out. We speculate that with close-to-threshold stimuli the arterial pulsations may serve as an endogenous noise source that may synchronise the sporadic discharge within the afferent population and thus facilitate the detection of weak stimuli. Citation: Birznieks I, Boonstra TW, Macefield VG (2012) Modulation of Human Muscle Spindle Discharge by Arterial Pulsations - Functional Effects and Consequences. PLoS ONE 7(4): e35091. doi:10.1371/journal.pone.0035091 Editor: Gennady Cymbalyuk, Georgia State University, United States of America Received September 4, 2011; Accepted March 13, 2012; Published April 17, 2012 Copyright: 2012 Birznieks et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This research was supported by a grant from the Australian Research Council (ARC; http://www.arc.gov.au/) and National Health and Medical Research Council (NHMRC; http://www.nhmrc.gov.au) of Australia TS0669860 and NHMRC Project Grant APP1029782. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: i.birznieks@uws.edu.au Introduction When the left ventricle of the heart ejects blood into the aorta the resultant pulse wave travels rapidly through the arterial system and reaches tissues throughout the body. Thus, mechanoreceptors inevitably become subjected to arterial pulsations when located in highly vascularised tissues. For example, almost half of all tactile afferents innervating the fingertips show cardiac modulation in some form and for some afferents even respiratory rhythmicity could be discerned [1,2]. Similarly, arterial pulsations are known to modulate the discharge activity in muscle spindles [3–7], and sometimes are capable of driving muscle spindle discharge, spindle firing being time locked to the arterial pulse in the absence of ongoing background activity. While McKeon and Burke [4] first described this phenomenon in recordings of human muscle spindles in a sample of 25 afferents, they only found three endings that were driven by the arterial pulse – the majority showed cardiac modulation that, the authors conclude, ‘‘are unlikely to be eliminated in the summed activity forming the population response.’’ One of the main objectives of these earlier studies was to investigate whether a synchronised response to arterial pulsations would compromise the capacity of spike-triggered averaging to measure the strength of synaptic connections between muscle spindle afferents and the spinal motoneurones [3,8,9]. Less attention has been drawn to the physiological consequences of such synchronised modulation by arterial pulsations. McKeon and Burke [4] suggested that that the arterial pulse could be a significant contributor to the discharge variability of muscle spindles and should be present in the population response, thereby limiting the information capacity of muscle spindle afferents. However, we do not know whether changes in either the magnitude of arterial pulsations, or the sensitivity of muscle spindles, during various physiological conditions translates into a physiologically significant change in discharge variability that may influence proprioceptive function. A reduction in the proprioceptive accuracy may require an increase PLoS ONE | www.plosone.org 1 April 2012 | Volume 7 | Issue 4 | e35091