Microglia enhance synapse activity to promote local network synchronization

Abstract

Microglia are highly motile immune-reactive cells that play integral roles in the response to brain infection and damage, and in the progression of various neurological diseases. During development, microglia also help sculpt neural circuits, via both promoting synapse formation and by targeting specific synapses for elimination and phagocytosis. Microglia are also active surveyors of neural circuits in the mature, healthy brain, although the functional consequences of such microglia-neuron contacts under these conditions is unclear. Using in vivo imaging of neurons and microglia in awake mice, we report here the functional consequences of microglia-synapse contacts. Direct contact between a microglial process and a single synapse results in a specific increase in the activity of that contacted synapse, and a corresponding increase in back-propagating action potentials along the parent dendrite. This increase in activity is not seen for microglia-synapse contacts when microglia are activated by chronic lipopolysaccharide (LPS) treatment. To probe how this microglia-synapse contact affects neural circuits, we imaged across larger populations of motor cortical neurons. When microglia were again activated by LPS (or partially ablated) there was a decrease in the extent to which neuronal activity was synchronized. Together our results demonstrate that interactions between physiological or resting microglia and synapses in the mature, healthy brain leads to an increase in neuronal activity and thereby helps to synchronize local populations of neurons. Our novel findings provide a plausible physical basis for understanding how alterations in immune status may impact on neural circuit plasticity and on cognitive behaviors such as learning.

Significance Statement Microglia, the sole immune cells in the central nervous system, make frequent contacts with synapses on dendritic spines, but the functional significance of these contact has remained elusive. In this study we use in vivo two photon imaging and demonstrate that microglia contact on spines increases synaptic activity. This microglia-induced increase in synaptic activity enhances the synchronization of neuronal populations. This increase synchrony is inhibited by microglial activation, proving a possible mechanistic basis for how immune status may impact on neural circuit function.