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bioRxiv · 10.1101/2020.12.05.413179

Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior

Horvath, T.·Yasumoto, Y.·Stoiljkovic, M.·Kim, J.·Sestan-Pesa, M.·Gao, X.-B.·Diano, S.
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Abstract

Microglia have been implicated in synapse remodeling by phagocytosis of synaptic elements in the adult brain. However, the underlying mechanism of such process is ill-defined. By examining microglia-neuronal interaction in the ventral hippocampus, we found a significant reduction in spine synapse number during the light phase of the light/dark cycle accompanied by increased microglial phagocytosis. This was followed by a transient rise in microglial production of reactive oxygen species (ROS) and uncoupling protein 2 (Ucp2) expression, which is a regulator of mitochondrial ROS generation. Conditional ablation of microglial Ucp2 hindered phasic elimination of spine synapses, increased accumulations of ROS and lysosome-lipid droplet complexes leading to hippocampal circuitry disruption assessed by electrophysiology, and, altered anxiety-like behavior. These observations unmasked a novel and chronotypical interaction between microglia and neurons involved in control of brain functions.

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Horvath, T., Yasumoto, Y., Stoiljkovic, M., Kim, J., Sestan-Pesa, M., Gao, X.-B., Diano, S.. 2020-12-06. Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior. https://doi.org/10.1101/2020.12.05.413179

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