Microglia as hunters or gatherers of brain synapses

IF 21.2 1区 医学 Q1 NEUROSCIENCES Nature neuroscience Pub Date : 2024-12-11 DOI:10.1038/s41593-024-01818-w
Marta Pereira-Iglesias, Joel Maldonado-Teixido, Alejandro Melero, Joaquin Piriz, Elena Galea, Richard M. Ransohoff, Amanda Sierra
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Abstract

Over a decade ago, it was discovered that microglia, the brain’s immune cells, engulf synaptic material in a process named microglial pruning. This term suggests that microglia actively sculpt brain circuits by tagging and phagocytosing unwanted synapses. However, live imaging studies have yet to demonstrate how microglial synapse elimination occurs. To address this issue, we propose a new conceptual framework distinguishing between two potential mechanisms of synapse elimination, culling and scavenging. During culling, microglia may use a contractile ring to sever the neuronal plasma membrane, removing the unwanted synapse. During scavenging, synapse elimination is neuronal-driven, and the neuronal plasma membrane fission machinery sheds off synapses that are later phagocytosed by microglia. We will discuss the current limitations of studying microglial synapse elimination and evaluate evidence supporting either culling or scavenging. Discerning between these mechanisms is essential for determining the therapeutic value of phagocytosis modulators in diseases with altered brain connectivity.

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Nature neuroscience
Nature neuroscience 医学-神经科学
CiteScore
38.60
自引率
1.20%
发文量
212
审稿时长
1 months
期刊介绍: Nature Neuroscience, a multidisciplinary journal, publishes papers of the utmost quality and significance across all realms of neuroscience. The editors welcome contributions spanning molecular, cellular, systems, and cognitive neuroscience, along with psychophysics, computational modeling, and nervous system disorders. While no area is off-limits, studies offering fundamental insights into nervous system function receive priority. The journal offers high visibility to both readers and authors, fostering interdisciplinary communication and accessibility to a broad audience. It maintains high standards of copy editing and production, rigorous peer review, rapid publication, and operates independently from academic societies and other vested interests. In addition to primary research, Nature Neuroscience features news and views, reviews, editorials, commentaries, perspectives, book reviews, and correspondence, aiming to serve as the voice of the global neuroscience community.
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