Bi-Directional Communication Between Neurons and Astrocytes Modulates Spinal Motor Circuits

Abstract

Evidence suggests that astrocytes are not merely supportive cells in the nervous system but may actively participate in the control of neural circuits underlying cognition and behavior. In this study, we examined the role of astrocytes within the motor circuitry of the mammalian spinal cord. Pharmacogenetic manipulation of astrocytic activity in isolated spinal cord preparations obtained from neonatal mice revealed astrocytederived, adenosinergic modulation of the frequency of rhythmic output generated by the locomotor central pattern generator (CPG) network. Live Ca 2+ imaging demonstrated increased activity in astrocytes during locomotor-related output and in response to the direct stimulation of spinal neurons. Finally, astrocytes were found to respond to neuronally-derived glutamate in a metabotropic glutamate receptor 5 (mGluR5) dependent manner, which in turn drives astrocytic modulation of the locomotor network. Our work identifies bi-directional signaling mechanisms between neurons and astrocytes underlying modulatory feedback control of motor circuits, which may act to constrain network output within optimal ranges for movement. LAY SUMMARYWe have investigated how astrocytes, a type of supportive cell within the nervous system, may be directly involved in the control of movements, such as walking (locomotion). We found that astrocytes are active participants in the neural circuits of the mammalian spinal cord that control locomotion. The function of astrocytes within these networks appears to relate to the modulation of locomotor speed. We also identify the chemical signaling pathways involved in a modulatory feedback loop between astrocytes and neurons. Our findings suggest that this bi-directional communication between astrocytes and neurons may act to constrain spinal motor circuits within operational ranges for desired movements.

Astrocytes promote ethanol-induced enhancement of intracellular Ca2+ signals through intercellular communication with neurons

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