Loss of the Compound Action Potential

an Electrophysiological, Biochemical and Morphological Study of Early Events in Axonal Degeneration in the C57BL/Ola Mouse

Jack Tsao, M. C. Brown, M. J. Carden, W. G. McLean, V. H. Perry

Research output: Contribution to journalArticle

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Abstract

In the C57BL/Ola (Ola) mouse strain there is a marked slowing of axonal disintegration during Wallerian degeneration. The locus of the mutation controlling this phenomenon (slow Wallerian degeneration‐ Wlds) has been mapped to chromosome 4, and its protective effect decreases with advancing age. Using biochemical, electrophysiological and histological techniques, the present study was undertaken to determine whether neurofilament phosphorylation and stability are altered or whether calcium‐activated proteases are absent in the sciatic nerves of Ola mice. A compound action potential was detectable only when neurofilaments were present and normal axonal architecture was seen. In 1‐month‐old Ola mice, compound action potentials and neurofilaments were still detectable at 21 days post‐transection, whereas both were undetectable by 2 days in BALB/c and C57BL/6J (6J) mice of the same age. Neurofilament levels declined faster with advancing Ola age, confirming previous results, whereas degeneration slowed in ageing BALB/c and 6J mice. In vitro and in vivo degeneration rates were comparable in BALB/c and 6J nerves. Ola nerves, however, showed more rapid decline in vitro than in vivo. Ola and BALB/c nerves frozen and then thawed and incubated in the presence of calcium ions and the ionophore A23187 were not resistant to degradation by intrinsic proteases. Even when a compound action potential could no longer be elicited, however, a majority of nerves still had >50% of myelinated and unmyelinated axons whose electron microscopic profiles appeared normal. Thus, it appears that the first event in Wallerian degeneration in the Ola mouse is a change at the plasma membrane‐a transected nerve becomes unable to conduct a compound action potential. Degeneration of the cytoskeleton is a later, separable event.

Original languageEnglish (US)
Pages (from-to)516-524
Number of pages9
JournalEuropean Journal of Neuroscience
Volume6
Issue number4
DOIs
StatePublished - Jan 1 1994

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Inbred C57BL Mouse
Action Potentials
Intermediate Filaments
Wallerian Degeneration
Peptide Hydrolases
Histological Techniques
Chromosomes, Human, Pair 4
Calcium Ionophores
Calcimycin
Sciatic Nerve
Cytoskeleton
Axons
Phosphorylation
Electrons
Ions
Mutation

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Loss of the Compound Action Potential : an Electrophysiological, Biochemical and Morphological Study of Early Events in Axonal Degeneration in the C57BL/Ola Mouse. / Tsao, Jack; Brown, M. C.; Carden, M. J.; McLean, W. G.; Perry, V. H.

In: European Journal of Neuroscience, Vol. 6, No. 4, 01.01.1994, p. 516-524.

Research output: Contribution to journalArticle

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abstract = "In the C57BL/Ola (Ola) mouse strain there is a marked slowing of axonal disintegration during Wallerian degeneration. The locus of the mutation controlling this phenomenon (slow Wallerian degeneration‐ Wlds) has been mapped to chromosome 4, and its protective effect decreases with advancing age. Using biochemical, electrophysiological and histological techniques, the present study was undertaken to determine whether neurofilament phosphorylation and stability are altered or whether calcium‐activated proteases are absent in the sciatic nerves of Ola mice. A compound action potential was detectable only when neurofilaments were present and normal axonal architecture was seen. In 1‐month‐old Ola mice, compound action potentials and neurofilaments were still detectable at 21 days post‐transection, whereas both were undetectable by 2 days in BALB/c and C57BL/6J (6J) mice of the same age. Neurofilament levels declined faster with advancing Ola age, confirming previous results, whereas degeneration slowed in ageing BALB/c and 6J mice. In vitro and in vivo degeneration rates were comparable in BALB/c and 6J nerves. Ola nerves, however, showed more rapid decline in vitro than in vivo. Ola and BALB/c nerves frozen and then thawed and incubated in the presence of calcium ions and the ionophore A23187 were not resistant to degradation by intrinsic proteases. Even when a compound action potential could no longer be elicited, however, a majority of nerves still had >50{\%} of myelinated and unmyelinated axons whose electron microscopic profiles appeared normal. Thus, it appears that the first event in Wallerian degeneration in the Ola mouse is a change at the plasma membrane‐a transected nerve becomes unable to conduct a compound action potential. Degeneration of the cytoskeleton is a later, separable event.",
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