Microglia contact induces synapse formation in developing somatosensory cortex

Abstract

Microglia are the immune cells of the central nervous system that play important roles in brain pathologies. Microglia also help shape neuronal circuits during development, via phagocytosing weak synapses and regulating neurogenesis. Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex, we demonstrate here that microglial contact with dendrites directly induces filopodia formation. This filopodia formation occurs only around postnatal day 8–10, a period of intense synaptogenesis and when microglia have an activated phenotype. Filopodia formation is preceded by contact-induced Ca2+ transients and actin accumulation. Inhibition of microglia by genetic ablation decreases subsequent spine density, functional excitatory synapses and reduces the relative connectivity from layer 4 neurons. Our data provide the direct demonstration of microglial-induced spine formation and provide further insights into immune system regulation of neuronal circuit development, with potential implications for developmental disorders of immune and brain dysfunction.

The Indispensable Roles of Microglia and Astrocytes during Brain Development

“…Thus, from this study, it can only be concluded that prenatal and immunologically activated microglia can have a negative effect on adult synaptic connections. Recently, it has been shown that in the developing somatosensory cortex, microglial contact with dendrites can induce synapse formation, mediated by calcium influx and actin accumulation at the contact site (Miyamoto et al, 2016). It is still largely unclear whether microglial contact was specific and necessary for the observed synapse formation.…”

Microglia mediate non‐cell‐autonomous cell death of retinal ganglion cells

“…To further confirm the neurotoxic role of activated microglia, we selectively ablated microglia using Iba1-tTA::DTA tetO/tetO (Iba1-DTA) mice (Miyamoto et al, 2016) (Figure 5a). To further confirm the neurotoxic role of activated microglia, we selectively ablated microglia using Iba1-tTA::DTA tetO/tetO (Iba1-DTA) mice (Miyamoto et al, 2016) (Figure 5a).…”

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

“…In the adult brain, the microglia is an important player in the regulation of synaptic plasticity [121,123,124] and in clearing newborn adult hippocampal progenitors [125]. Thus, there is evidence of the involvement of microglia in the control of long-term potentiation [126][127][128] long-term depression [129], synaptogenesis [130,131], and in sensing and eliminating defunct synapses [119].…”