When Little Means a Lot: Impact of a Brief Early-life Motor Training on Mouse Neuromuscular Development

ABSTRACT In this study, we aimed to determine the impact of an increase in motor activity during the highly plastic period of development of the motor spinal cord and hindlimb muscles in newborn mice. A swim training regimen, consisting of two sessions per day for two days, was conducted in 1 and 2-day-old (P1, P2) pups. P3-trained pups showed a faster acquisition of a four-limb swimming pattern, accompanied by dysregulated gene expression in the lateral motor column, alterations in the intrinsic membrane properties of motoneurons (MNs) and synaptic plasticity, as well as increased axonal myelination in motor regions of the spinal cord. Network-level changes were also observed, as synaptic events in MNs and spinal noradrenaline and serotonin contents were modified by training. At the muscular level, slight changes in neuromuscular junction morphology and myosin subtype expression in hindlimb muscles were observed in trained animals. Furthermore, the temporal sequence of acquiring the adult-like swimming pattern and postural development in trained pups showed differences persisting until almost the second postnatal week. A very short motor training performed just after birth is thus able to induce functional adaptation in the developing neuromuscular system that could persist several days. This highlights the vulnerability of the neuromuscular apparatus during development and the need to evaluate carefully the impact of any given sensorimotor procedure when considering its application to improve motor development or in rehabilitation strategies.