Paolicelli, R. C. et al. Microglia states and nomenclature: a field at its crossroads. Neuron 110, 3458–3483 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eyo, U. & Molofsky, A. V. Defining microglial–synapse interactions. Science 381, 1155–1156 (2023).

Article  CAS  PubMed  Google Scholar 

Boivin, J. R. & Nedivi, E. Functional implications of inhibitory synapse placement on signal processing in pyramidal neuron dendrites. Curr. Opin. Neurobiol. 51, 16–22 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mordelt, A. & de Witte, L. D. Microglia-mediated synaptic pruning as a key deficit in neurodevelopmental disorders: hype or hope? Curr. Opin. Neurobiol. 79, 102674 (2023).

Article  CAS  PubMed  Google Scholar 

Citri, A. & Malenka, R. C. Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology 33, 18–41 (2008).

Article  PubMed  Google Scholar 

Monday, H. R., Younts, T. J. & Castillo, P. E. Long-term plasticity of neurotransmitter release: emerging mechanisms and contributions to brain function and disease. Annu. Rev. Neurosci. 41, 299–322 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lisman, J. Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20160260 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Turrigiano, G. G. The self-tuning neuron: synaptic scaling of excitatory synapses. Cell 135, 422–435 (2008).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yuste, R. & Bonhoeffer, T. Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu. Rev. Neurosci. 24, 1071–1089 (2001).

Article  CAS  PubMed  Google Scholar 

Kasai, H., Ziv, N. E., Okazaki, H., Yagishita, S. & Toyoizumi, T. Spine dynamics in the brain, mental disorders and artificial neural networks. Nat. Rev. Neurosci. 22, 407–422 (2021).

Article  CAS  PubMed  Google Scholar 

Nagappan-Chettiar, S., Yasuda, M., Johnson-Venkatesh, E. M. & Umemori, H. The molecular signals that regulate activity-dependent synapse refinement in the brain. Curr. Opin. Neurobiol. 79, 102692 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yasuda, M., Nagappan-Chettiar, S., Johnson-Venkatesh, E. M. & Umemori, H. An activity-dependent determinant of synapse elimination in the mammalian brain. Neuron 109, 1333–1349 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Papa, M. & Segal, M. Morphological plasticity in dendritic spines of cultured hippocampal neurons. Neuroscience 71, 1005–1011 (1996).

Article  CAS  PubMed  Google Scholar 

Henson, M. A., Tucker, C. J., Zhao, M. & Dudek, S. M. Long-term depression-associated signaling is required for an in vitro model of NMDA receptor-dependent synapse pruning. Neurobiol. Learn. Mem. 138, 39–53 (2017).

Article  CAS  PubMed  Google Scholar 

He, H., Shen, W., Zheng, L., Guo, X. & Cline, H. T. Excitatory synaptic dysfunction cell-autonomously decreases inhibitory inputs and disrupts structural and functional plasticity. Nat. Commun. 9, 2893 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Lu, W., Bushong, E. A., Shih, T. P., Ellisman, M. H. & Nicoll, R. A. The cell-autonomous role of excitatory synaptic transmission in the regulation of neuronal structure and function. Neuron 78, 433–439 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Blackman, M. P., Djukic, B., Nelson, S. B. & Turrigiano, G. G. A critical and cell-autonomous role for MeCP2 in synaptic scaling up. J. Neurosci. 32, 13529–13536 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chang, C.-W., Wilkerson, J. R., Hale, C. F., Gibson, J. R. & Huber, K. M. Distinct stages of synapse elimination are induced by burst firing of CA1 neurons and differentially require MEF2A/D. eLife 6, e26278 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Paolicelli, R. C. et al. Synaptic pruning by microglia is necessary for normal brain development. Science 333, 1456–1458 (2011).

Article  CAS  PubMed  Google Scholar 

Xu, R. et al. Human iPSC-derived mature microglia retain their identity and functionally integrate in the chimeric mouse brain. Nat. Commun. 11, 1577 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu, R. et al. Developing human pluripotent stem cell-based cerebral organoids with a controllable microglia ratio for modeling brain development and pathology. Stem Cell Reports 16, 1923–1937 (2021).

Google Scholar 

Schafer, D. P. et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691–705 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Gottfried, E. et al. Expression of CD68 in non-myeloid cell types. Scand. J. Immunol. 67, 453–463 (2008).

Article  CAS  PubMed  Google Scholar 

Stillman, J. M. et al. Lipofuscin-like autofluorescence within microglia and its impact on studying microglial engulfment. Nat. Commun. 14, 7060 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Burns, J. C. et al. Differential accumulation of storage bodies with aging defines discrete subsets of microglia in the healthy brain. eLife 9, e57495 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Scott-Hewitt, N. et al. Local externalization of phosphatidylserine mediates developmental synaptic pruning by microglia. EMBO J. 39, e105380 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tremblay, M.-È., Lowery, R. L. & Majewska, A. K. Microglial interactions with synapses are modulated by visual experience. PLoS Biol. 8, e1000527 (2010).

Article  PubMed  PubMed Central  Google Scholar 

Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S. & Nabekura, J. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. 29, 3974–3980 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pfeiffer, T., Avignone, E. & Nägerl, U. V. Induction of hippocampal long-term potentiation increases the morphological dynamics of microglial processes and prolongs their contacts with dendritic spines. Sci. Rep. 6, 32422 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Miyamoto, A. et al. Microglia contact induces synapse formation in developing somatosensory cortex. Nat. Commun. 7, 12540 (2016).

Article  CAS