Massive loss of proprioceptive Ia synapses in rat spinal motoneurons after nerve crush injuries in the postnatal period.

Peripheral nerve injuries (PNI) induce the retraction from the ventral horn of the synaptic collaterals of Ia afferents injured in the nerve, effectively removing Ia synapses from a-motoneurons. The loss of Ia input impairs functional recovery and could explain, in part, better recovery after PNIs with better Ia synaptic preservation. Synaptic losses correlate with injury severity, speed and efficiency of muscle reinnervation and requires ventral microglia activation. It is unknown whether this plasticity is age dependent. In neonates, axotomized motoneurons and sensory neurons undergo apoptosis, but after postnatal day 10 most survive. This goal was to analyze vesicular glutamate transporter 1 (VGLUT1) labeled Ia synapses (which might also include II afferents) after nerve crush in 10 day old Sprague Dawley rats, a PNI causing little Ia/II synapse loss in adult. We confirmed fast and efficient reinnervation of leg muscles, however a massive number of VGLUT1/Ia/II synapses were permanently lost. This synapse loss was similar to that after more severe nerve injuries involving full transection in adults. In adults, disappearance of ventrally directed Ia/II collaterals targeting α-motoneurons was associated with a prolonged microglia reaction and a CCR2 mechanism that included infiltration of CCR2 blood immune cells. By contrast, microgliosis after p10 injuries was fast, resolved in about a week, and there was no evidence of peripheral immune cell infiltration. We conclude that VGLUT1/Ia/II synapse loss in young animals differs in mechanism, perhaps associated with higher microglia synaptic pruning activity at this age and results in larger losses after milder nerve injuries. Significance statement Synaptic plasticity in spinal motor circuits induced by nerve injuries can be rather permanent and hinder motor and sensory function recovery, even when experimental manipulations are designed for fast and efficient regeneration and target innervation. One input particularly affected is the Ia afferent synapse on α-motoneurons. The degree of loss of this input depends on injury severity and correlates with varying efficiencies while reinnervating peripheral targets. In here we demonstrate that the loss is also age dependent, being higher in the young. The enhanced synaptic pruning capabilities of microglia during critical windows of high synaptic plasticity at early age, might contribute to augment synaptic circuit reorganizations.