Effect of Sympathetic Neurotransmitters on Muscle Spindle Afferent Sensitivity to Muscle Stretch in Adult Mice

Abstract

The primary sensory input for proprioception, or the sense of body position in space, comes from muscle spindle afferents, which are mechanoreceptors that relay information about changes in muscle length. The muscle spindle is also innervated by sympathetic neurons, but the role of this sympathetic innervation on muscle spindle function is not well understood. Here we test the hypothesis that muscle spindle afferents will exhibit decreased firing in response to muscle stretch following exposure to the sympathetic neurotransmitters norepinephrine and epinephrine. To test this hypothesis we used an ex vivo mouse muscle‐nerve preparation. We recorded muscle spindle afferent firing activity during ramp‐and‐hold stretch and sinusoidal vibration before and after the addition of norepinephrine, epinephrine, or adrenergic receptor agonists. We observed significantly decreased firing during the end of stretch after both norepinephrine (100 µm, n=6) and epinephrine (30 µm, n=6). To identify the adrenergic receptor(s) involved, we also tested two ɑ2 adrenergic receptor agonists, Clonidine and Dexmedetomidine, and the ɑ1 receptor agonist phenylephrine. Both ɑ2 receptor agonists caused a decrease in muscle spindle afferent firing (1 mM clonidine, n=8 decreased firing; 100 µm dexmedetomidine, n=3). Phenylephrine had no significant effect on muscle spindle afferent firing (100 µm n=2; 30 µm n=6). These results show direct effects of sympathetic neurotransmitters on muscle spindle afferent stretch sensitivity and further support the hypothesis that sympathetic innervation of the muscle spindle plays an important role in modulating muscle spindle afferent activity and therefore motor control. Future studies will investigate the location of the adrenergic receptor(s) mediating this effect as well as the mechanism of action.