Spinal Motor Circuit Synaptic Plasticity after Peripheral Nerve Injury Depends on Microglia Activation and a CCR2 Mechanism

Peripheral nerve injuries can lead to lasting motor problems, even after the nerves heal. The brain and spinal cord circuits change after the injury, but the exact reasons are not well understood. This study looks at how these changes happen in the spinal cord, specifically how nerve damage causes a loss of certain connections that are important for muscle reflexes. The study shows that after a nerve injury, specific immune cells in the spinal cord, called microglia, become active. Then other immune cells, known as CCR2 cells, move into the area. These immune cells cause a loss of synaptic connections, which affects how muscles respond to stretch. This loss of connections contributes to motor deficits after nerve regeneration. By using mice that allowed the research team to visualize the microglia and CCR2 cells, the scientists were able to demonstrate that both the activation of microglia and the presence of CCR2 cells are needed to remove certain synapses, impacting motor circuit function following nerve injuries.

• 1
  Microglia activation around damaged motoneurons starts and peaks within two weeks after nerve damage.
• 2
  VGLUT1 synapses, which are important for muscle reflexes, are rescued when the microglial reaction is reduced or when CCR2 is removed.
• 3
  Both activation of ventral microglia and a CCR2-dependent mechanism are necessary for removing VGLUT1 synapses and for changes in Ia-circuit function after nerve injuries.