Microglia: Dynamic Mediators of Synapse Development and Plasticity

Abstract

Neuronal communication underlies all brain activity and the genesis of complex behavior. Emerging research has revealed an unexpected role for immune molecules in the development and plasticity of neuronal synapses. Moreover microglia, the resident immune cells of the brain, express and secrete immune-related signaling molecules that alter synaptic transmission and plasticity in the absence of inflammation. When inflammation does occur, microglia modify synaptic connections and synaptic plasticity required for learning and memory. Here we review recent findings demonstrating how the dynamic interactions between neurons and microglia shape the circuitry of the nervous system in the healthy brain and how altered neuron-microglia signaling could contribute to disease.

Figure 1. Microglial-mediated Synaptic Pruning

A. Confocal image of a microglia (green) in the lateral geniculate nucleus (LGN) surrounded by synaptic inputs from both eyes (blue and red) that were visualized by intraocular injections of different colored anterograde tracers. For more details please see [10]. B. In wild type mice, microglial engulfment of synaptic material is observed at postnatal day (P)5 as depicted in the cartoon. Elimination of synapses (referred to as synaptic pruning) is required for circuit refinement, as schematized by segregation of red and blue inputs into distinct territories (P30). C. Insufficient synaptic pruning as observed in C1q, C3, CR3 deficient mice results in impaired circuit refinement. Lack of CX3CR1 has been associated with reduced synaptic pruning in other brain regions [9, 14].

Figure 2. Microglia Surveillance

A. Two photon image of a microglia (green) and the dendrites of a single patch-filled CA1 pyramidal neuron (red) in a hippocampal brain slice from a CX3CR1-EGFP mouse. The 3D rendering was made using ImageJ. For more details please see [26]. B. The cartoons illustrate the surveillance by microglial processes under baseline conditions. The blue and grey shaded regions represent the positions of microglial processes at different time points. High neuronal activity triggers enhanced surveillance, which is schematized by the movement from blue to light grey over time.