Abstract Introduction The understanding of the neurophysiological mechanisms underlying movement control can be much furthered using computational models of the neuromusculoskeletal system. Biologically based multi-scale neuromusculoskeletal models have a great potential to provide new theories and explanations related to mechanisms behind muscle force generation at the molecular, cellular, synaptic, and systems levels. Albeit some efforts have been made to investigate how neurodegenerative diseases alter the dynamics of individual elements of the neuromuscular system, such diseases have not been analyzed from a systems viewpoint using multi-scale models. Overview and Perspectives This perspective article synthesizes what has been done in terms of multi-scale neuromuscular development and points to a few directions where such models could be extended so that they can be useful in the future to discover early predictors of neurodegenerative diseases, as well as to propose new quantitative clinical neurophysiology approaches to follow the course of improvements associated with different therapies (drugs or others). Concluding Remarks Therefore, this article will present how existing biologically based multi-scale models of the neuromusculoskeletal system could be expanded and adapted for clinical applications. It will point to mechanisms operating at different levels that would be relevant to be considered during model development, along with implications for interpreting experimental results from neurological patients.

INTRODUCTION: The learning of core concepts in neuroscience can be reinforced by a hands-on approach, either experimental or computer-based. In this work, we present a web-based multi-scale neuromuscular simulator that is being used as a teaching aid in a campus-wide course on the Principles of Neuroscience. METHODS: The simulator has several built-in individual models based on cat and human biophysics, which are interconnected to represent part of the neuromuscular system that controls leg muscles. Examples of such elements are i) single neurons, representing either motor neurons or interneurons mediating reciprocal, recurrent and Ib inhibition; ii) afferent fibers that can be stimulated to generate spinal reflexes; iii) muscle unit models, generating force and electromyogram; and iv) stochastic inputs, representing the descending volitional motor drive. RESULTS: Several application examples are provided in the present report, ranging from studies of individual neuron responses to the collective action of many motor units controlling muscle force generation. A subset of them was included in an optional homework assignment for Neuroscience and Biomedical Engineering graduate students enrolled in the course cited above at our University. Almost all students rated the simulator as a good or an excellent learning tool, and approximately 90% declared that they would use the simulator in future projects. CONCLUSION: The results allow us to conclude that multi-scale neuromuscular simulator is an effective teaching tool. Special features of this free teaching resource are its direct usability from any browser (http://remoto.leb.usp.br/), its user-friendly graphical user interface (GUI) and the preset demonstrations.