Function and Dysfunction of Microglia during Brain Development: Consequences for Synapses and Neural Circuits

Abstract

Many diverse factors, ranging from stress to infections, can perturb brain homeostasis and alter the physiological activity of microglia, the immune cells of the central nervous system. Microglia play critical roles in the process of synaptic maturation and brain wiring during development. Any perturbation affecting microglial physiological function during critical developmental periods could result in defective maturation of synaptic circuits. In this review, we critically appraise the recent literature on the alterations of microglial activity induced by environmental and genetic factors occurring at pre- and early post-natal stages. Furthermore, we discuss the long-lasting consequences of early-life microglial perturbation on synaptic function and on vulnerability to neurodevelopmental and psychiatric disorders.

Microglial Implication in Parkinson’s Disease: Loss of Beneficial Physiological Roles or Gain of Inflammatory Functions?

“…In particular, homeostatic microglia contribute to synaptogenesis, synaptic pruning, and myelination (Schafer and Stevens, 2015; Kaur et al, 2017; Li and Barres, 2017; Paolicelli and Ferretti, 2017; Tay et al, 2017; Low and Ginhoux, 2018). Microglia are also required for the adaptation of the brain and behavior to the living environment (Tremblay et al, 2011; Schafer and Stevens, 2015; Tay et al, 2017, 2018).…”

Developmental roles of microglia: A window into mechanisms of disease

“…• Synaptic pruning and refinement (Ji et al, ; Miyamoto et al, ; Wu et al, ; Paolicelli and Ferretti, ).…”

Spatial impact of microglial distribution on dynamics of dendritic spines

“…Recent studies have revealed that microglia play critical roles in synapse formation and elimination during development and circuit refinement after maturation (reviewed in Paolicelli & Ferretti, ). Previous studies proposed that microglial density was related to synaptic density and functional maturation of neural circuits (Hoshiko, Arnoux, Avignone, Yamamoto, & Audinat, ; Paolicelli et al., ).…”

“…Disruption of microglial purinergic receptors led to a perturbation of ocular dominance plasticity (Sipe et al., ). Several reports have suggested microglial abnormalities in animal models and human neurodevelopmental diseases patients (Suzuki et al., ; reviewed in Paolicelli & Ferretti, ). These observations indicate the importance of microglia in regulating synapses both in normal neural circuit development and in pathological conditions.…”