The mechanotransduction protein STOML3 is required for proprioceptor plasticity following peripheral nerve...

Nerve regeneration is associated with the plasticity of sensory neurons such that even muscle afferents directed to the skin form mechanosensitive receptive fields appropriate for the new target. STOML3 is an essential mechanotransduction component in many cutaneous mechanoreceptors. Here, we asked whether STOML3 is required for functional and anatomical plasticity following peripheral nerve regeneration. We used a cross-anastomosis model adapted to the mouse, in which the medial gastrocnemius nerve was redirected to innervate hairy skin previously occupied by the sural nerve. We recorded from muscle afferents innervating the skin and found that in wild-type mice their receptive properties were largely identical to normal skin mechanoreceptors. However, in mice lacking STOML3, muscle afferents largely failed to form functional mechanosensitive receptive fields, despite making anatomically appropriate endings in the skin. Our tracing experiments demonstrated that muscle afferents from both wild-type and stoml3 mutant mice display remarkable anatomical plasticity, forming new somatotopically appropriate synaptic terminals in the region of the dorsal horn representing the sural nerve territory. The dramatic reduction in stimulus-evoked activity from the cross-anastomosed gastrocnemius nerve in stoml3 mutant mice did not prevent central anatomical plasticity. Our results have identified a molecular factor required for functional plasticity following peripheral nerve injury.