Motor Unit Activity During Neonatal Synapse Elimination

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Balice-Gordon IBN-9982233 A fundamental question in neuroscience is how connections are made and maintained among neurons and their targets. A number of studies over the last 25 years have shown that neural wiring is exquisitely sensitive to experience, which is translated into neural activity. Thus changes in neural activity can have a profound impact on neural connectivity. Despite this appreciation, the underlying mechanisms are poorly understood. We use the synaptic connection between motor neurons and muscle fibers, called neuromuscular junctions, as a model system to understand how neural activity changes neural connectivity. We propose to study how the relative firing patterns of motor neurons change during postnatal development, and whether such change might modulate changes in synaptic connections at developing neuromuscular junctions. During late embryonic and early postnatal life, skeletal muscle fibers undergo an activity-dependent, competitive transition from multiple to single innervation. In developing muscle and brain, competition among motor units is modulated by their relative patterns of activity. Temporally correlated patterns of motor unit activity might be present before competition begins, while asynchronous activity may lead to the loss of the least active inputs. While this hypothesis is supported by many experimental manipulations, no studies have determined the relative activity patterns of motor neurons that impinges on neuromuscular synapses in vivo. These experiments will also further our understanding of how neural activity shapes patterns of synaptic connectivity, not only during development, but throughout life.