Reciprocal Regulation between Resting Microglial Dynamics and Neuronal Activity In Vivo

• Published in: Developmental cell 2012-12, Vol.23 (6), p.1189-1202
• Main Authors: Li, Ying, Du, Xu-fei, Liu, Chang-sheng, Wen, Zi-long, Du, Jiu-lin
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Communication; Cell differentiation, maturation, development, hematopoiesis; Cell Movement; Cell physiology; Connexins - metabolism; Danio rerio; Down-Regulation; Fundamental and applied biological sciences. Psychology; Microglia - cytology; Microglia - metabolism; Microglia - physiology; Microglia - ultrastructure; Molecular and cellular biology; Neurons - cytology; Neurons - metabolism; Neurons - physiology; Neurons - ultrastructure; rac GTP-Binding Proteins - metabolism; Signal Transduction; Superior Colliculi - cytology; Superior Colliculi - physiology; Time-Lapse Imaging; Zebrafish; Zebrafish Proteins - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2012.10.027

Microglia are the primary immune cells in the brain. Under physiological conditions, they typically stay in a “resting” state, with ramified processes continuously extending to and retracting from surrounding neural tissues. Whether and how such highly dynamic resting microglia functionally interact with surrounding neurons are still unclear. Using in vivo time-lapse imaging of both microglial morphology and neuronal activity in the optic tectum of larval zebrafish, we found that neuronal activity steers resting microglial processes and facilitates their contact with highly active neurons. This process requires the activation of pannexin-1 hemichannels on neurons. Reciprocally, such resting microglia-neuron contact reduces both spontaneous and visually evoked activities of contacted neurons. Our findings reveal an instructive role for neuronal activity in resting microglial motility and suggest the function for microglia in homeostatic regulation of neuronal activity in the healthy brain. ► Resting microglial processes dynamically contact neuronal soma via bulbous endings ► Neuronal activity instructs resting microglial processes to contact active neurons ► Pannexin-1 hemichannel in neurons and Rac in microglia are required for this effect ► Resting microglia-neuron contact downregulates the activity of contacted neurons Little is known about the role of resting microglia in the healthy brain. Looking in vivo in zebrafish, Li et al. uncover reciprocal regulation between neurons and resting microglia in which neuronal activity provokes the formation of microglial contacts that, in turn, downregulate the activity of contacted neurons.