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Microglia-mediated synaptic pruning in neural circuit remodeling: multidimensional control in homeostasis and

Zheng Liu1,2, Wu-Lan Ao1,2, Ai-Di Luo1,2

  • 1Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.

BMC Medicine
|July 9, 2026
PubMed
Abstract

Insights

Microglia, the brain's immune cells, regulate synaptic plasticity and circuit stability. Their dysfunction in neurological diseases leads to pathological synapse loss, impairing cognitive function.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are the central nervous system's resident immune cells.
  • They play critical roles in synaptic plasticity and maintaining neural circuit homeostasis.

Purpose of the Study:

  • To review the mechanisms by which microglia influence synaptic structure and function.
  • To explore the role of microglial dysfunction in neurological diseases.
  • To highlight therapeutic strategies targeting microglial modulation.

Main Methods:

  • Literature review of microglial functions in synaptic remodeling.
  • Analysis of microglial roles in physiological and pathological conditions.
  • Examination of factors modulating microglial activity (circadian rhythms, microbiota-gut-brain axis).

Main Results:

  • Microglia shape synapses via dynamic interactions, pruning, epigenetic regulation, ECM remodeling, metabolic adaptation, and glial communication.
  • Physiological microglial functions support circuit refinement, synaptic stability, and cognition.
  • Microglial dysfunction in Alzheimer's disease and schizophrenia contributes to pathological synapse loss and impaired circuit function.

Conclusions:

  • Microglial heterogeneity and dynamic state transitions are crucial for understanding synaptic remodeling.
  • Targeted modulation of microglia offers potential therapeutic strategies for neurological diseases.
Keywords:
Circadian rhythmExcitation/inhibition balanceMetabolic reprogrammingMicrobiota-gut-brain axisMicrogliaNeurodegenerative diseasesSynaptic plasticitySynaptic pruning

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