Synaptic Plasticity on Motoneurons After Axotomy: A Necessary Change in Paradigm

Peripheral nerve injuries cause motoneurons to undergo changes in their synaptic inputs, accompanied by a neuroinflammatory response involving microglia and astrocytes. The functional importance and underlying mechanisms of these changes remain unclear. This review proposes dividing synaptic plasticity around injured motoneurons into two processes: rapid, microglia-independent synapse shedding that reverses after muscle reinnervation, and a slower, microglia-dependent mechanism that permanently alters spinal cord circuitry. The slower mechanism eliminates sensory Ia afferent proprioceptor axon collaterals, reconfiguring ventral horn motor circuits to function without direct sensory feedback. The reversible changes occur while motoneurons regenerate and involve a transient reduction in fast synaptic activity, possibly replaced by slow GABA depolarizations for regenerative mechanisms.

• 1
  Synaptic plasticity around axotomized motoneurons should be divided into two distinct processes: a rapid cell-autonomous, microglia-independent shedding of synapses and a slower microglia-dependent mechanism that permanently alters spinal cord circuitry.
• 2
  The slower mechanism fully eliminates from the ventral horn the axon collaterals of peripherally injured and regenerating sensory Ia afferent proprioceptors, reconfiguring ventral horn motor circuitries to function after regeneration without direct sensory feedback from muscle.
• 3
  Reversible synaptic changes on the cell bodies occur only while motoneurons are regenerating and generally result in a transient reduction of fast synaptic activity that is probably replaced by embryonic-like slow GABA depolarizations.