Impaired neuromuscular transmission of the tibialis anterior in a rodent model of hypertonia.

Early onset hypertonia is characteristic of developmental neuromotor disorders, including cerebral palsy (CP). The spa transgenic mouse displays early onset spasticity, abnormal gait and motor impairments that are remarkably similar to symptoms of human CP. Previously, we showed that spa mice have fewer motor neurons innervating the TA. An expanded innervation ratio may result in increased susceptibility to neuromuscular transmission failure (NMTF). We assessed NMTF in an ex vivo TA muscle-nerve preparation from spa and wildtype (WT) mice by comparing forces elicited by nerve versus muscle stimulation. TA muscle innervation ratio was assessed by counting the number of muscle fibers and dividing by the number of TA motor neurons. Muscle fiber cross sectional areas was also assessed in the TA muscle. We observed that NMTF was immediately present in spa mice, worsened with repetitive stimulation, and was associated with increased innervation ratio. These changes were concomitant with reduced TA muscle fiber cross sectional area in spa mice compared to WT. Early-onset hypertonia is associated with increased innervation ratio and impaired neuromuscular transmission. These disturbances may exacerbate the underlying gait abnormalities present in individuals with hypertonia.