Abstract
Emerging evidence suggests that synaptic dysfunction occurs prior to neuronal loss in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS). Therefore, monitoring synaptic activity during early stages of neurodegeneration may provide valuable information for the development of diagnostic and/or therapeutic strategies. Here, we describe an electrophysiological method routinely applied in our laboratory for investigating synaptic activity of the neuromuscular junction (NMJ), the synaptic connection between motoneurons and skeletal muscles. Using conventional intracellular sharp electrodes, both spontaneous synaptic activity (miniature end-plate potentials) and evoked synaptic activity (end-plate potentials) can be readily recorded in acutely isolated nerve–muscle preparations. This method can also be adapted to various simulation protocols for studying short-term plasticity of neuromuscular synapses.
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References
Stalberg, E., Schwartz, M. S., and Trontelj, J. V. (1975) Single fibre electromyography in various processes affecting the anterior horn cell, J Neurol Sci 24, 403–415.
Killian, J. M., Wilfong, A. A., Burnett, L., Appel, S. H., and Boland, D. (1994) Decremental motor responses to repetitive nerve stimulation in ALS, Muscle Nerve 17, 747–754.
Similowski, T., Attali, V., Bensimon, G., Salachas, F., Mehiri, S., Arnulf, I., Lacomblez, L., Zelter, M., Meininger, V., and Derenne, J. P. (2000) Diaphragmatic dysfunction and dyspnoea in amyotrophic lateral sclerosis, Eur Respir J 15, 332–337.
Fischer, L. R., Culver, D. G., Tennant, P., Davis, A. A., Wang, M., Castellano-Sanchez, A., Khan, J., Polak, M. A., and Glass, J. D. (2004) Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man, Exp Neurol 185, 232–240.
Frey, D., Schneider, C., Xu, L., Borg, J., Spooren, W., and Caroni, P. (2000) Early and selective loss of neuromuscular synapse subtypes with low sprouting competence in motoneuron diseases, J Neurosci 20, 2534–2542.
Bruijn, L. I., Becher, M. W., Lee, M. K., Anderson, K. L., Jenkins, N. A., Copeland, N. G., Sisodia, S. S., Rothstein, J. D., Borchelt, D. R., Price, D. L., and Cleveland, D. W. (1997) ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions, Neuron 18, 327–338.
Bruijn, L. I., Houseweart, M. K., Kato, S., Anderson, K. L., Anderson, S. D., Ohama, E., Reaume, A. G., Scott, R. W., and Cleveland, D. W. (1998) Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1, Science 281, 1851–1854.
Kennel, P. F., Finiels, F., Revah, F., and Mallet, J. (1996) Neuromuscular function impairment is not caused by motor neurone loss in FALS mice: an electromyographic study, Neuroreport 7, 1427–1431.
Williamson, T. L., and Cleveland, D. W. (1999) Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons, Nat Neurosci 2, 50–56.
Wong, F., Fan, L., Wells, S., Hartley, R., Mackenzie, F. E., Oyebode, O., Brown, R., Thomson, D., Coleman, M. P., Blanco, G., and Ribchester, R. R. (2009) Axonal and neuromuscular synaptic phenotypes in Wld(S), SOD1(G93A) and ostes mutant mice identified by fiber-optic confocal microendoscopy, Mol Cell Neurosci 42, 296–307.
Coleman, P. D., and Yao, P. J. (2003) Synaptic slaughter in Alzheimer’s disease, Neurobiol Aging 24, 1023–1027.
Nelson, P. G. (2005) Activity-dependent synapse modulation and the pathogenesis of Alzheimer disease, Curr Alzheimer Res 2, 497–506.
Selkoe, D. J. (2002) Alzheimer’s disease is a synaptic failure, Science 298, 789–791.
Raff, M. C., Whitmore, A. V., and Finn, J. T. (2002) Axonal self-destruction and neurodegeneration, Science 296, 868–871.
Chen, F., Sugiura, Y., Myers, K. G., Liu, Y., and Lin, W. (2010) Ubiquitin carboxyl-terminal hydrolase L1 is required for maintaining the structure and function of the neuromuscular junction, Proc Natl Acad Sci USA 107, 1636–1641.
McArdle, J. J., Angaut-Petit, D., Mallart, A., Bournaud, R., Faille, L., and Brigant, J. L. (1981) Advantages of the triangularis sterni muscle of the mouse for investigations of synaptic phenomena, J Neurosci Methods 4, 109–115.
Angaut-Petit, D., Molgo, J., Connold, A. L., and Faille, L. (1987) The levator auris longus muscle of the mouse: a convenient preparation for studies of short- and long-term presynaptic effects of drugs or toxins, Neurosci Lett 82, 83–88.
Carlsen, R. C., Larson, D. B., and Walsh, D. A. (1985) A fast-twitch oxidative-glycolytic muscle with a robust inward calcium current, Can J Physiol Pharmacol 63, 958–965.
Lomo, T., and Rosenthal, J. (1972) Control of ACh sensitivity by muscle activity in the rat, J Physiol 221, 493–513.
Balice-Gordon, R. J., and Thompson, W. J. (1988) The organization and development of compartmentalized innervation in rat extensor digitorum longus muscle, J Physiol 398, 211–231.
Balice-Gordon, R. J., and Thompson, W. J. (1988) Synaptic rearrangements and alterations in motor unit properties in neonatal rat extensor digitorum longus muscle, J Physiol 398, 191–210.
Ribchester, R. R. (2009) Mammalian neuromuscular junctions: modern tools to monitor synaptic form and function, Curr Opin Pharmacol 9, 297–305.
Aickin, C. C., Betz, W. J., and Harris, G. L. (1989) Intracellular chloride and the mechanism for its accumulation in rat lumbrical muscle, J Physiol 411, 437–455.
Clark, A. W., Bandyopadhyay, S., and DasGupta, B. R. (1987) The plantar nerves-lumbrical muscles: a useful nerve-muscle preparation for assaying the effects of botulinum neurotoxin, J Neurosci Methods 19, 285–295.
Harris, G. L., and Betz, W. J. (1987) Evidence for active chloride accumulation in normal and denervated rat lumbrical muscle, J Gen Physiol 90, 127–144.
Ross, J. J., Duxson, M. J., and Harris, A. J. (1987) Neural determination of muscle fibre numbers in embryonic rat lumbrical muscles, Development 100, 395–409.
Liley, A. W. (1956) An investigation of spontaneous activity at the neuromuscular junction of the rat, J Physiol 132, 650–666.
Cruz, L. J., Gray, W. R., Olivera, B. M., Zeikus, R. D., Kerr, L., Yoshikami, D., and Moczydlowski, E. (1985) Conus geographus toxins that discriminate between neuronal and muscle sodium channels, J Biol Chem 260, 9280–9288.
Hong, S. J., and Chang, C. C. (1989) Use of geographutoxin II (mu-conotoxin) for the study of neuromuscular trans-mission in mouse, Br J Pharmacol 97, 934–940.
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Sugiura, Y., Chen, F., Liu, Y., Lin, W. (2011). Electrophysiological Characterization of Neuromuscular Synaptic Dysfunction in Mice. In: Manfredi, G., Kawamata, H. (eds) Neurodegeneration. Methods in Molecular Biology, vol 793. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-328-8_26
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DOI: https://doi.org/10.1007/978-1-61779-328-8_26
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