Neuron-Glia Signaling in Synapse Elimination

Annu Rev Neurosci. 2019 Jul 8:42:107-127. doi: 10.1146/annurev-neuro-070918-050306.

Abstract

Maturation of neuronal circuits requires selective elimination of synaptic connections. Although neuron-intrinsic mechanisms are important in this process, it is increasingly recognized that glial cells also play a critical role. Without proper functioning of these cells, the number, morphology, and function of synaptic contacts are profoundly altered, resulting in abnormal connectivity and behavioral abnormalities. In addition to their role in synaptic refinement, glial cells have also been implicated in pathological synapse loss and dysfunction following injury or nervous system degeneration in adults. Although mechanisms regulating glia-mediated synaptic elimination are still being uncovered, it is clear this complex process involves many cues that promote and inhibit the removal of specific synaptic connections. Gaining a greater understanding of these signals and the contribution of different cell types will not only provide insight into this critical biological event but also be instrumental in advancing knowledge of brain development and neural disease.

Keywords: astrocyte; disease; microglia; molecular mechanism; myelinating glia; neuronal activity; synaptic pruning.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Astrocytes / physiology
  • Biological Evolution
  • Central Nervous System / embryology*
  • Central Nervous System / growth & development
  • Cues
  • Exosomes / physiology
  • Humans
  • Invertebrates / embryology
  • Microglia / physiology
  • Morphogenesis
  • Myelin Sheath / physiology
  • Nerve Degeneration / physiopathology*
  • Nervous System Diseases / physiopathology*
  • Neuroglia / physiology*
  • Neuromuscular Junction / embryology
  • Neurons / physiology*
  • Peripheral Nervous System / embryology*
  • Peripheral Nervous System / growth & development
  • Synapses / pathology
  • Synapses / physiology*