Depletion of microglia in developing cortical circuits reveals its critical role in glutamatergic synapse development, functional connectivity, and critical period plasticity. Issue 10 (28th June 2020)

• Record Type: Journal Article
• Authors: Ma, Xiaokuang; Chen, Ke; Cui, Yuehua; Huang, Guanqun; Nehme, Antoine; Zhang, Le; Li, Handong; Wei, Jing; Liong, Katerina; Liu, Qiang; Shi, Lingling; Wu, Jie; Qiu, Shenfeng
• Is Part Of: Journal of neuroscience research. Volume 98:Issue 10(2020)
• Page Start: 1968
• Page End: 1986
• Publication Date: 2020-06-28
• Subjects: autism -- circuit connectivity -- cortical plasticity -- electrophysiology -- microglia -- neurodevelopmental disorders -- RRID:AB_10712685 -- RRID:AB_2631098 -- RRID:AB_561053 -- RRID:AB_839504; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.24641
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract: Microglia populate the early developing brain and mediate pruning of the central synapses. Yet, little is known on their functional significance in shaping the developing cortical circuits. We hypothesize that the developing cortical circuits require microglia for proper circuit maturation and connectivity, and as such, ablation of microglia during the cortical critical period may result in a long‐lasting circuit abnormality. We administered PLX3397, a colony‐stimulating factor 1 receptor inhibitor, to mice starting at postnatal day 14 and through P28, which depletes >75% of microglia in the visual cortex (VC). This treatment largely covers the critical period (P19‐32) of VC maturation and plasticity. Patch clamp recording in VC layer 2/3 (L2/3) and L5 neurons revealed increased mEPSC frequency and reduced amplitude, and decreased AMPA/NMDA current ratio, indicative of altered synapse maturation. Increased spine density was observed in these neurons, potentially reflecting impaired synapse pruning. In addition, VC intracortical circuit functional connectivity, assessed by laser scanning photostimulation combined with glutamate uncaging, was dramatically altered. Using two photon longitudinal dendritic spine imaging, we confirmed that spine elimination/pruning was diminished during VC critical period when microglia were depleted. Reduced spine pruning thus may account for increased spine density and disrupted connectivity of VC circuits. Lastly, using single‐unit recording combined with monocular deprivation, we found that ocular dominance plasticity in the VC was obliterated during the critical period as a result of microglia depletion. These data establish a critical role of microglia in developmental cortical synapse pruning, maturation, functional connectivity, and critical period plasticity. Abstract : Depletion of microglia during cortical critical period profoundly alters glutamatergic synapse developmental trajectory Microglia is critical for visual cortex spine pruning, circuit refinement, intracortical connectivity, and critical period plasticity