Mechanisms of structural plasticity of adult synapses by astrocytic phagocytosis

Abstract

In the adult brain, synapses undergo constant formation and elimination. However, the exact function and DBS 이준혁. 별아교세포의 성체 시냅스 포식에 의한 구조적 가소성 연구. 생명과학과. 2022년. 134+vi 쪽. 지도교수: 정원석. (영문 논문) Joon-Hyuk Lee. Mechanisms of Structural Plasticity of adult synapses by Astrocytic Phagocytosis. 2022. 134+vi pages. Advisor: Won-Suk Chung. (Text in English) ii regulatory process of synapse elimination in the adult brain are largely unknown. Here, we reveal a significant role of astrocytic phagocytosis in the diverse region of adult brain. By utilizing mCherry-eGFP phagocytosis reporters, we find that synapses are eliminated by astrocytic phagocytosis in the adult hippocampal CA1, primary visual cortex and olfactory bulb. Surprisingly, our data show that astrocyte-mediated synapse elimination is critical for maintaining synaptic homeostasis as well as synapse remodeling in response to sensory alteration and neurogenesis. Furthermore, knocking-out the phagocytic receptor Megf10 in adult astrocytes reduces their ability to eliminate excitatory synapses, and as a result, induces the deficits in the synapse remodeling. Taken together, our data provide strong evidence that astrocytes eliminate the unwanted excitatory synaptic connections in the adult brain through MEGF10-dependent phagocytosis, and that this astrocytic function is critical for structural synaptic plasticity.