A computer simulation of conduction in demyelinated nerve fibres

Abstract

SUMMARY1. The theoretical effects ofdemyelination on conduction ofa propagated impulse have been examined in a computer simulated myelinated nerve fibre. Demyelination was simulated by increasing the capacitance and conductance of the myelin sheath of individual internodes or parts of internodes.2. Internodal conduction time increased as myelin thickness was decreased. The increase in internodal conduction time became more precipitous as the myelin became thinner. Propagation continued past a single demyelinated internode until myelin thickness was uniformly reduced to less than 2-7 % of normal myelin thickness.3. Paranodal demyelination was more effective in slowing impulse conduction than was uniform demyelination of an entire internode with an equivalent rise in overall internodal capacitance and conductance.4. The effects on conduction of demyelination of two adjacent internodes or of two internodes separated by a normal internode were more than the sum of the effects of demyelination of each internode individually.5. Propagation across a severely demyelinated internode was blocked with an increase in internal sodium concentration which had a trivial effect on conduction in a normal fibre.6. Propagation across a severely demyelinated internode was blocked

Conduction in Segmentally Demyelinated Mammalian Central Axons

“…Although conduction was observed in axons that were thinly remyelinated, it was never observed in axons with internodes of fewer than five lamellae of compact myelin. This observation adds weight to previous theoretical studies ( Koles and Rasminsky, 1972;Halter and Blight, 1996), which have suggested that very thin sheaths may preclude successf ul conduction. A preliminary examination of axons undergoing remyelination has revealed very few sheaths of only a few lamellae (our unpublished observations), and it may be that during myelinogenesis myelin compaction is delayed until a relatively thick sheath can be made quite rapidly.…”

CNS Myelin Paranodes Require Nkx6-2 Homeoprotein Transcriptional Activity for Normal Structure

“…Although internodal loops, flaps, thin myelin, and naked axons are widespread in these animals, our data indicate that outer lateral loops in most sheaths reach the paranode and form axoglial junctions sufficiently well to enable appropriate targeting of NF155, caspr, contactin, K ϩ channels, NF186, and Na ϩ channels. Previous studies showed that only a few wraps of compact myelin membrane are necessary for reliable nerve conduction in CNS (Koles and Rasminsky, 1972); together, these data account for the relatively minor physiological consequences for null mutants without the need to invoke compensatory mechanisms from other neural Nkx family members. Nevertheless, the subtlety of this phenotype does not diminish the importance of the gene regulatory network uncovered in the current study.…”

“…From an electrophysiological standpoint, the most important aspect of this interaction is the assembly and maintenance of heterotypic, adhesive junctions between axons and myelin sheaths (Koles and Rasminsky, 1972). These axoglial junctions, composed of neuronal and oligodendroglial components, serve several essential functions: they flank and define nodes of Ranvier, they impede the movement of interstitial ions and other molecules into the periaxonal space, and they compartmentalize the axolemma into at least three distinct subdomains: nodes of Ranvier, paranodes, and juxtaparanodes (for review, see Arroyo et al, 2001;Bhat, 2003;Salzer, 2003).…”

Auditory-Nerve Responses to Varied Inter-Phase Gap and Phase Duration of the Electric Pulse Stimulus as Predictors for Neuronal Degeneration

“…On the other hand, a longer PD (950 μs) may introduce significant influence of the leaky integrator, which means that more charge is needed to compensate membrane leakage over the length of the phase duration (Moon et al 1993). In that respect, a stronger "leaky" effect for the deafened groups might be expected since the demyelination associated with SGC degeneration (Agterberg et al 2008) causes leakier cell membranes (Koles and Rasminsky 1972;Spoendlin 1984). Instead, we did not find differences between healthy and degenerating SGC populations.…”

“…Probably the SGCs that are additionally recruited by the increased IPG have higher excitation thresholds, thereby enhancing the dynamic range. Given that this increase in dynamic range only occurs for deafened animals, these high individual thresholds may correspond to degenerating SGCs, or SGCs with a degenerated myelin sheath (Koles and Rasminsky 1972;Spoendlin 1984).…”