Exploration of neuromuscular plasticity: an examination of acetylcholine receptor and skeletal muscle fiber adaptations

Muscle is an example of a beautifully orchestrated biological system whose main role is to convey a chemical stimulus into a mechanical response. Skeletal muscles carry out the function of moving the bones of the skeleton. Skeletal muscles display remarkable levels of adaptability and plasticity. The regulation of neuromuscular plasticity is influenced by signals coming from the motor neuron and from within the muscles. In this thesis, different transgenic and surgical mice models are used to investigate key aspects of muscle plasticity. Firstly, transgenic mice expressing a calmodulin-binding peptide are used to demonstrate that calmodulin regulates the aggregation of acetylcholine receptors. Secondly, the roles of Nuclear Factor of activated-Tcells (NFAT) transcription factors are investigated in adaptive muscle growth using mice knockouts for these transcription factors. The results presented indicate that NFATc2 and NFATc3 are essential for muscle hypertrophy and that they have distinct roles in the regulation of muscle growth. Thirdly, novel roles for the nerve-derived trophic factor agrin are explored in healthy and deteriorating muscles. Overall, the results presented in this thesis provide original information on the regulation of muscle plasticity and serve to point to novel potential targets in the regulation of various neuromuscular diseases