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Microglia Are Dispensable for Developmental Dendrite Pruning of Mitral Cells in Mice
Tetsushi Niiyama1, Satoshi Fujimoto2, Takeshi Imai2
1Graduate School of Medical Sciences, Kyushu University, 812-8582, Fukuoka, Japan.
Abstract:
During early development, neurons in the brain often form excess synaptic connections. Later, they strengthen some connections while eliminating others to build functional neuronal circuits. In the olfactory bulb, a mitral cell initially extends multiple dendrites to multiple glomeruli but eventually forms a single primary dendrite through the activity-dependent dendrite pruning process. Recent studies have reported that microglia facilitate synapse pruning during the circuit remodeling in some systems. It has remained unclear whether microglia are involved in the activity-dependent dendrite pruning in the developing brains. Here, we examined whether microglia are required for the developmental dendrite pruning of mitral cells in mice. To deplete microglia in the fetal brain, we treated mice with a colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, from pregnancy. Microglia were reduced by >90% in mice treated with PLX5622. However, dendrite pruning of mitral cells was not significantly affected. Moreover, we found no significant differences in the number, density, and size of excitatory synapses formed in mitral cell dendrites. We also found no evidence for the role of microglia in the activity-dependent dendrite remodeling of layer 4 (L4) neurons in the barrel cortex. In contrast, the density of excitatory synapses (dendritic spines) in granule cells in the olfactory bulb was significantly increased in mice treated with PLX5622 at postnatal day (P) 6, suggesting a role for the regulation of dendritic spines. Our results indicate that microglia do not play a critical role in activity-dependent dendrite pruning at the neurite level during early postnatal development in mice.
Insights
Microglia do not critically impact developmental dendrite pruning in the mouse brain. This study found no significant effect on mitral cell dendrite refinement or synapse elimination after microglia depletion.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Neurons form excess connections early in development, later refining them into functional circuits.
- Microglia are known to prune synapses in some developing systems, but their role in dendrite pruning is unclear.
- Mitral cells in the olfactory bulb undergo activity-dependent dendrite pruning to establish single primary dendrites.
Purpose of the Study:
- To investigate the role of microglia in the activity-dependent dendrite pruning of mitral cells in developing mice.
- To determine if microglia are essential for the refinement of neuronal circuits during early brain development.
Main Methods:
- Mice were treated with a colony-stimulating factor 1 receptor (CSF1R) inhibitor (PLX5622) during gestation to deplete microglia (>90% reduction).
- Dendrite pruning of mitral cells was assessed.
- Excitatory synapse number, density, and size were analyzed.
- Dendrite remodeling in layer 4 neurons and dendritic spine density in olfactory bulb granule cells were also examined.
Main Results:
- Microglia depletion did not significantly affect mitral cell dendrite pruning.
- No significant differences were observed in the number, density, or size of excitatory synapses on mitral cell dendrites.
- No role for microglia was found in the activity-dependent dendrite remodeling of layer 4 neurons.
- A significant increase in excitatory synapses (dendritic spines) was observed in granule cells of microglia-depleted mice.
Conclusions:
- Microglia are not essential for activity-dependent dendrite pruning of mitral cells during early postnatal development in mice.
- While microglia may influence dendritic spine density, they do not appear to play a critical role in neurite-level dendrite pruning.
- These findings clarify the specific role of microglia in synaptic and dendritic remodeling during neural circuit formation.
