The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord^1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.

牵张反射是运动系统的基本组成部分，它协调运动背后的协调肌肉收缩。这个过程的核心是肌梭 （MS），这是专门受体，可以精细地适应导静脉内肌纤维内的张力波动。MS 中的张力变化触发了一系列神经元事件，包括感觉 Ia 型传入神经的初始去极化，随后导致脊髓 ^1,2 内运动神经元的激活。这种神经元级联反应以肌肉收缩的执行而告终，强调了肌肉骨骼和神经系统之间假定的闭环机制。相比之下，我们在这里报告了在 MS 中发现的具有独特分子和功能特征的新巨噬细胞种群，这些特征表达合成和释放谷氨酸的机制。使用小鼠交叉遗传学与光遗传学和电生理学，我们表明 MS 巨噬细胞 （MSMP） 的激活在毫秒时间尺度上驱动本体感觉神经元放电。MSMP 通过激发 MS 的谷氨酸依赖性机制激活脊髓回路、运动神经元和肌肉。此外，MSMP 通过增加谷氨酰胺酶的表达来响应神经和肌肉激活，使它们能够将肌细胞在肌肉收缩过程中释放的摄取谷氨酰胺转化为谷氨酸。后肢肌肉中 MSMP 的选择性沉默或耗竭破坏了对牵张反射的调节以产生力和感觉反馈校正，损害了小鼠的运动策略。我们的结果确定了一种新的细胞成分 MSMP，它直接调节神经活动和肌肉收缩。 MSMP 的谷氨酸介导的信号传导及其对感觉线索的动态反应为我们对感觉和运动动作的理解引入了一个新的维度，有可能在影响感觉运动功能的情况下提供创新的治疗方法。