New Function of Microglia: Promotion of Filopodia and Hence Synaptogenesis during Early Brain Development

New Function of Microglia: Promotion of Filopodia and Hence Synaptogenesis during Early Brain Development

A recent study published in Nature Communications reveals that the brain microglia influences the developing brain through induction of filopodia creation, thus, shaping neuronal connectivity and synapses formation.

Microglia are important components of the neuro-immune interactions in the brain. As the resident macrophage cells, the microglial cells provide the main immune defense in the central nervous system.

Recent evidence indicates that microglia also contributes to the normal brain physiology, including neurogenesis and the promotion of synapse formation. Thus, for example, adding microglial cells to hippocampal cultures results in the increase of the number of dendritic spines, an effect mediated via the release of interleukin (IL) -10.

Little is known, however, how, in fact, microglia trigger or modify synapse formation, and whether this effect is directly dependent on microglia-neurons interactions.

In the Nature Communications report, Akiko Miyamoto and colleagues, provided a direct demonstration of how microglia-neuronal interactions can shape neuronal morphology and connectivity, via the induction of filopodia formation.

Of note, synapses develop from filopodia that according to the authors represent “labile, postsynaptic protrusions that may stabilize and develop into mature spines” (cf. Refs. 22, 25, 34 and 35, the Miyamoto et al. study).

Using in vivo multiphoton imaging of layer 2/3 pyramidal neurons in the developing somatosensory cortex in mice, the authors report that the direct contact between microglia and dendrites induced a rapid appearance and growth of filopodia, through Ca2+ accumulation and actin recruitment. Moreover, blocking microglia activity caused fewer functional synapses formation and less dendritic arborization.

Importantly, the authors observed that this microglia contact-induced filopodia was only observed at the 8th to 10th days, corresponding to an ameboid-like microglia (activated state), which can involve the release of soluble factors such as IL-10, tumor necrosis factor (TNF)-α and nerve growth factors.

Thus, it appears that Miyamoto et al. provide the first evidence that the microglia contact induces filopodia and, then, synapses formation, revealing a new physiologic function for microglia.

The authors suggest that “filopodia formation by microglia promotes the maturation of specific neuronal circuit connections through the formation of functional mature synapses”.

They also believe that these mechanisms may also contribute to psychiatric disorders, such as schizophrenia and autism where “disruptions in synapse number, morphology or function” are reported.

Source: Nat Commun, 2016 Aug 25; 7:12540. doi: 10.1038/ncomms12540
Read More: Nature Communications

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Source: Cover Image: Scheme of microglia functions during synaptogenesis: Sequence of proposed cellular events during synapse formation: Microglial contact initiates a rise in local [Ca2+]i resulting in actin accumulation and filopodia formation. Some filopodia find presynaptic partners and mature into functional synapses; From: Figure 6, Miyamoto et al., Nat Commun, 2016 Aug 25; 7:12540; http://www.nature.com/articles/ncomms12540#results; Creative Commons; Public Domain.

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