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

• Published in: bioRxiv
• Main Authors: Yasumoto, Yuki, Stoiljkovic, Milan, Jung Dae Kim, Sestan-Pesa, Matija, Xiao-Bing, Gao, Diano, Sabrina, Horvath, Tamas L
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 07.12.2020; Cold Spring Harbor Laboratory
• Edition: 1.2
• Subjects: Anxiety; Electrophysiology; Hippocampus; Microglia; Mitochondria; Mitochondrial uncoupling protein 2; Neuroscience; Phagocytosis; Reactive oxygen species
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2020.12.05.413179

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. Competing Interest Statement The authors have declared no competing interest. Footnotes * Author order was mixed up. It is now corrected.