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Senthilkumar Deivasigamani1, Mariya T Miteva1,2, Silvia Natale1,3

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Complement signaling promotes neuronal elimination in the developing brain, not synaptic pruning. Mice lacking Complement receptor 3 showed deficits in neuron removal, impacting cortical development and adult connectivity.

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Area of Science:

  • Neuroscience
  • Immunology
  • Developmental Biology

Background:

  • Complement signaling is implicated in synaptic pruning by microglia.
  • Its broader role in brain development, beyond the retino-thalamic system, is not fully understood.

Purpose of the Study:

  • To investigate the role of complement signaling in general synaptic pruning and neuronal elimination in the developing mouse cortex.
  • To determine the function of Complement receptor 3 (CR3) in microglia-mediated developmental processes.

Main Methods:

  • Utilized knockout mice lacking Complement receptor 3 (CR3).
  • Assessed synaptic pruning, axon elimination, and neuronal elimination in the developing mouse cortex.
  • Analyzed cortical thickness and functional connectivity in adult mice.

Main Results:

  • Mice lacking CR3 did not exhibit deficits in synaptic pruning or axon elimination.
  • CR3 deficiency led to impaired perinatal neuronal elimination in the cortex.
  • These mice showed increased cortical thickness and enhanced adult functional connectivity.

Conclusions:

  • Complement signaling, via CR3, promotes neuronal elimination during cortical development.
  • CR3 is crucial for eliminating excess neurons, influencing cortical structure and function.