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Updated: Mar 15, 2026
Author Spotlight: In Vitro Co-Culture Model for Studying Microglia-Neuronal Interactions in Disease Conditions
Published on: July 26, 2024
Microglia contact induces synapse formation in developing somatosensory cortex
Akiko Miyamoto1,2, Hiroaki Wake1,2,3,4, Ayako Wendy Ishikawa3,5
1Division of Homeostatic Development, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
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 Ca(2+) 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.
Insights
Microglia, the brain's immune cells, directly prompt new spine formation on developing neurons. This immune cell activity is crucial for building healthy neural circuits and may impact developmental disorders.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Microglia are central nervous system immune cells involved in brain pathologies and neural circuit development.
- They influence neuronal development through processes like synaptic pruning and neurogenesis regulation.
Purpose of the Study:
- To investigate the direct impact of microglial contact on neuronal dendrite development in the somatosensory cortex.
- To elucidate the role of microglia in synapse formation during early postnatal development.
Main Methods:
- In vivo multiphoton imaging of layer 2/3 pyramidal neurons in developing mouse somatosensory cortex.
- Observation of microglial-neuronal interactions and dendritic spine formation.
- Genetic ablation of microglia to assess functional consequences on synaptic development.
Main Results:
- Microglial contact with dendrites directly induces filopodia formation, a precursor to dendritic spines.
- This phenomenon occurs during a critical period (postnatal days 8-10) of synaptogenesis when microglia are activated.
- Microglial ablation leads to reduced spine density, fewer functional excitatory synapses, and altered neuronal connectivity.
Conclusions:
- Microglia actively regulate neuronal circuit development by directly inducing dendritic spine formation.
- This study provides direct evidence for immune system involvement in shaping synaptic architecture.
- Findings have implications for understanding developmental disorders involving immune and brain dysfunction.
