Broadhead Matthew J, Miles Gareth B
School of Psychology and Neuroscience, University of St Andrews, St Andrews, United Kingdom.
Front Cell Neurosci. 2020 Feb 27;14:30. doi: 10.3389/fncel.2020.00030. eCollection 2020.
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 astrocyte-derived, adenosinergic modulation of the frequency of rhythmic output generated by the locomotor central pattern generator (CPG) network. Live Ca 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.
有证据表明，星形胶质细胞不仅是神经系统中的支持细胞，还可能积极参与对认知和行为背后神经回路的控制。在本研究中，我们研究了星形胶质细胞在哺乳动物脊髓运动回路中的作用。对从新生小鼠获得的离体脊髓制剂中星形胶质细胞活性进行药物遗传学操纵，揭示了星形胶质细胞衍生的腺苷能对运动中枢模式发生器（CPG）网络产生的节律性输出频率的调节作用。实时钙成像显示，在运动相关输出期间以及对脊髓神经元的直接刺激作出反应时，星形胶质细胞的活性增加。最后，发现星形胶质细胞以代谢型谷氨酸受体5（mGluR5）依赖的方式对神经元衍生的谷氨酸作出反应，这反过来又驱动星形胶质细胞对运动网络的调节。我们的工作确定了神经元和星形胶质细胞之间双向信号传导机制，其构成运动回路调节性反馈控制的基础，这可能有助于将网络输出限制在运动的最佳范围内。
