Neonatal infraorbital nerve crush-induced CNS synaptic plasticity and functional

19 Infraorbital nerve (ION) transection in neonatal rats leads to disruption of whisker20 specific neural patterns (barrelettes), conversion of functional synapses into silent 21 synapses and reactive gliosis in the brainstem trigeminal principal nucleus (PrV). Here 22 we tested the hypothesis that neonatal peripheral nerve crush injuries permit better 23 functional recovery of associated central nervous system synaptic circuitry compared to 24 nerve transection. We developed an in vitro whisker pad-trigeminal ganglion (TG)25 brainstem preparation in neonatal rats and tested functional recovery in the PrV following 26 ION crush. Intracellular recordings revealed that 68% of TG cells innervate the whisker 27 pad. We used the proportion of whisker pad-innervating TG cells as an index of ION 28 function. The ION function was blocked by ~64%, immediately after mechanical crush, 29 then it recovered beginning after 3 days post-injury and was complete by 7 days. We used 30 this reversible nerve-injury model to study peripheral nerve injury-induced CNS synaptic 31 plasticity. In the PrV, the incidence of silent synapses increased to ~3.5 times of control 32 value by 2-3 days post-injury and decreased to control levels by 5-7 days post-injury. 33 Peripheral nerve injury-induced reaction of astrocytes and microglia in the PrV was also 34 reversible. Neonatal ION crush disrupted barrelette formation and functional recovery 35 was not accompanied by de novo barrelette formation, most likely due to occurrence of 36 recovery post critical period (P3) for pattern formation. Our results suggest that nerve 37 crush is more permissive for successful regeneration and reconnection (collectively 38 referred to as “recovery” here) of the sensory inputs between the periphery and the 39