Myo-GDNF increases non-functional polyinnervation of reinnervated mouse muscle

Glial cell line-derived neurotrophic factor (GDNF) promotes neuronal survival and influences the development and function of synaptic connections. To test the role of GDNF on the stabilisation of synapses, we examined reinnervated neuromuscular junctions in myo-GDNF mice that over-express GDNF under control of a myogenin promoter. The level of polyneuronal innervation was increased following reinnervation in these mice, although many converging inputs were extremely fine and contained few neurofilaments. Electrophysiological experiments confirmed that some inputs were weak or non-functional by showing that the increased morphological levels of polyneuronal innervation were not reflected in the functional responses of endplates to nerve stimulation. Thus, myo-GDNF over-expression enhances reinnervation, but at the expense of both neurofilament integrity, and functional reliability.