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J Neurophysiol 97: 1846-1856, 2007. First published December 6, 2006; doi:10.1152/jn.00904.2006
0022-3077/07 $8.00
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INNOVATIVE METHODOLOGY

Method for Counting Motor Units in Mice and Validation Using a Mathematical Model

Lora A. Major, Janka Hegedus, Douglas J. Weber, Tessa Gordon and Kelvin E. Jones

Centre for Neuroscience, University of Alberta, Edmonton, Canada

Submitted 24 August 2006; accepted in final form 4 December 2006

Weakness and atrophy are clinical signs that accompany muscle denervation resulting from motor neuron disease, peripheral neuropathies, and injury. Advances in our understanding of the genetics and molecular biology of these disorders have led to the development of therapeutic alternatives designed to slow denervation and promote reinnervation. Preclinical in vitro research gave rise to the need of a method for measuring the effects in animal models. Our goal was to develop an efficient method to determine the number of motor neurons making functional connections to muscle in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). We developed a novel protocol for motor unit number estimation (MUNE) using incremental stimulation. The method involves analysis of twitch waveforms using a new software program, ITS-MUNE, designed for interactive calculation of motor unit number. The method was validated by testing simulated twitch data from a mathematical model of the neuromuscular system. Computer simulations followed the same stimulus-response protocol and produced waveform data that were indistinguishable from experiments. We show that our MUNE protocol is valid, with high precision and small bias across a wide range of motor unit numbers. The method is especially useful for large muscle groups where MUNE could not be done using manual methods. The results are reproducible across naïve and expert analysts, making it suitable for easy implementation. The ITS-MUNE analysis method has the potential to quantitatively measure the progression of motor neuron diseases and therefore the efficacy of treatments designed to alleviate pathologic processes of muscle denervation.


Address for reprint requests and other correspondence: K. E. Jones, Department of Biomedical Engineering, Faculty of Medicine and Dentistry, University of Alberta, 8308-114 Street, Research Transition Facility 1098, Edmonton, AB T6G 2V2, Canada (E-mail: kejones{at}ualberta.ca)




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J. Hegedus, C. T. Putman, N. Tyreman, and T. Gordon
Preferential motor unit loss in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis
J. Physiol., July 15, 2008; 586(14): 3337 - 3351.
[Abstract] [Full Text] [PDF]




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