The muscle stretch reflex, which is mediated by sensory receptors known as muscle spindles, is a contractile response to stretch that helps to maintain muscle tone and control movement. Stretch of the muscle spindle activates sensory nerve fibres that synapse directly with motor neurons in the spinal cord, in what was previously thought to be a closed-loop neuromuscular circuit. However, Yan et al. now report the identification of a unique population of muscle spindle macrophages that regulate this circuit by releasing glutamate.

Optogenetic stimulation of muscle spindle macrophages in mouse hindlimb muscle to induce their depolarization resulted in an electrical response in sensory and motor neurons of the stretch reflex at a millisecond timescale, leading to muscle contraction. Optogenetic stimulation of muscle spindle macrophages expressing the light-sensitive chloride channel NpHR3, which causes hyperpolarization and inhibits activity, reduced the size of the contractile response to muscle elongation, which suggests that muscle spindle macrophages regulate the amplitude of the stretch reflex in response to muscle stretch.