Contributions of microglia to structural synaptic plasticity

Abstract

Synaptic plasticity critically depends on reciprocal interactions between neurons and glia. Among glial cells, microglia represent approximately 10% of the total brain cell population serve as the brain's resident macrophage, and help to modulate neural activity. Because of their special role in the brain's immune response, microglia are involved in the pathological progression of neurodegenerative disorders such as Alzheimer's disease (AD). However, microglia also are surveyors of the brain's health and continuously contact dendritic spines to regulate structural synaptic changes. This review summarizes our current understanding of neuronal-microglial signals that affect neural function at the synapse. Here, we examine the role of microglia in neuronal synapses in pathological brains and specifically focus on in vivo studies using 2-photon microscopy. Furthermore, because the role of microglia in AD progression is controversial, we outline the interaction between neurons and microglia in pathological conditions such as AD.

Keywords: Alzheimer’s disease (AD); Microglia; Synaptic plasticity; neuron-microglia crosstalk.

Figure 1

Signaling crosstalk between neurons and microglia under physiological conditions. This is a simplified list of the neuron-microglia signaling pathway. Abbreviations: BDNF, brain-derived neurotrophic factor; CCL21, chemokine (C-C motif) ligand 21; CD200, cluster of differentiation 200; Aβ, amyloid beta; TGF-β, transforming growth factor-beta; CSF-1, macrophage-colony stimulating factor-1; IL-1β, interleukin-1 beta; GABA, gamma-aminobutyric acid; ATP, adenosine triphosphate; CXCR3, chemokine (C-X-C motif) receptor 3; RAGE, receptor for advanced glycation end products; LRP1, low density lipoprotein receptor-related protein 1; P2R, purinergic receptor; CX3CR1, CX3C chemokine receptor 1; CR3, complement receptor (modified from Kettenmann et al70).

Figure 2. Physiological roles of microglia in neuronal circuits

Schematic diagram indicating the physiological functions of microglia in neuronal circuits. Microglia play a role in maintaining neuronal circuits during development (a) and neurogenesis (b) by regulating programmed cell death or by phagocytosis of adult cells. (c) In addition, microglia act as surveyors of brain health by interacting with dendritic spines. (d) Microglia can modulate synaptic transmission by secreting molecules such as cytokines, hormones, and growth factors (adapted from Wake et al71).