Muscle spindle-derived neurotrophin 3 regulates synaptic connectivity between muscle sensory and motor neurons.

Ia afferents induce the formation of muscle spindles prenatally and maintain them postnatally. To address whether spindles, in turn, regulate the function of Ia afferents, we examined Egr3-null mutant mice (Egr3-/-), in which muscle spindles degenerate progressively after birth. Egr3-/- mice develop gait ataxia, scoliosis, resting tremors, and ptosis, suggesting a defect in proprioception. Despite the normal morphological appearance of peripheral and central sensory projections, we observed a profound functional deficit in the strength of sensory-motor connections in Egr3-/- mice. Muscle spindles in Egr3-/- mice do not express NT3. Intramuscular injections of NT3 to Egr3-/- mice during the postnatal period restored sensory-motor connections. Thus, NT3 derived from muscle spindles regulates the synaptic connectivity between muscle sensory and motor neurons.