Carlos B. Mantilla, M.D., Ph.D.

My research interests address the control of breathing and the recovery of respiratory function following injuries including spinal cord injury. One of the fundamental mechanisms regulating motor function is the efficacy of neuromuscular transmission. We recently found that neurotrophins are important regulators of neuromuscular transmission in the diaphragm muscle, the most important inspiratory muscle in many species including humans. Neurotrophins are synthesized by neurons and muscle fibers and may be released in an activity-dependent fashion at the neuromuscular junction. The efficacy of neuromuscular transmission effects the final output of the motor system and force generation. At the present time, the in vivo regulation of synaptic efficacy at the neuromuscular junction remains unknown. To explore these issues, our studies have as their aims: 1) to determine the influence of neurotrophins on synaptic vesicle recycling at type-identified diaphragm neuromuscular junctions; 2) to determine the signaling pathways involved in neurotrophin-mediated regulation of neuromuscular transmission; and 3) to determine the role of neurotrophins in the recovery of motor function following spinal cord injury. These studies will provide great insight into the mechanisms regulating synaptic efficacy at a well-characterized synapse (the diaphragm neuromuscular junction), but these are likely common and important mechanisms that regulate other synapses throughout the nervous system. Thus, these studies should have broad application in the treatment of neuromuscular disorders including not only spinal cord injury, but also prolonged immobility and paralysis, chronic pain conditions and central nervous system diseases.