Macrophages excite muscle spindles with glutamate to bolster locomotion
Year: 2024
Type: article
Abstract: 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 fibers. The tension variation in the MS triggers a series of neuronal events; an initial depolarization of sensory type Ia afferents that subsequently causes the activation of a motoneurons within the spinal cord. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. In contrast, surprisingly here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the muscle spindle that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of muscle spindle macrophages (MSMP) drives proprioceptive sensory neuron firing at a millisecond timescale. This subsequently activates spinal circuits, motor neurons, and muscles via a glutamate-dependent mechanism. Additionally, we found that MSMP can also respond to the activation of the stretch reflex circuitry by increasing the expression of glutaminase, enabling them to convert the glutamine released by myocytes during muscle contraction into glutamate. 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 introduces a novel dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.
Source: Nature
Authors: Yuyang Yan, Nuria Antolin, Luming Zhou, Luyang Xu, Irene Lisa Vargas, Carlos Daniel Gomez, Guiping Kong, Ilaria Palmisano, Yi Yang, Jessica Chadwick, Franziska Müller, Anthony M. J. Bull, Cristina Lo Celso, Guido Primiano, Serenella Servidei, Jean François Perrier, Carmelo Bellardita, Simone Di Giovanni
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,290
OpenAlex ID: W4405030716