The plasticity of nerve fibers: the prolonged effects of polarization of afferent fibers

Abstract

The review surveys various aspects of the plasticity of nerve fibres, in particular the prolonged increase in their excitability evoked by polarization, focusing on a long-lasting increase in the excitability of myelinated afferent fibres traversing the dorsal columns of the spinal cord. We review the evidence that increased axonal excitability (i) follows epidurally applied direct current as well as relatively short (5 or 10 ms) current pulses and synaptically evoked intrinsic field potentials; (ii) critically depends on the polarization of branching regions of afferent fibres at the sites where they bifurcate and give off axon collaterals entering the spinal grey matter in conjunction with actions of extrasynaptic GABAA membrane receptors; and (iii) shares the feature of being activity-independent with the short-lasting effects of polarization of peripheral nerve fibres. A comparison between the polarization evoked sustained increase in the excitability of dorsal column fibres and spinal motoneurons (plateau potentials) indicates the possibility that they are mediated by partly similar membrane channels (including non-inactivating type L Cav++ 1.3 but not Na+ channels) and partly different mechanisms. We finally consider under which conditions trans-spinally applied DC (tsDCS) might reproduce the effects of epidural polarization on dorsal column fibres and the possible advantages of increased excitability of afferent fibres for the rehabilitation of motor and sensory functions after spinal cord injuries.

Long‐term modulation of the axonal refractory period

“…When the refractory period was shortened by epidural depolarisation, the second of the paired stimuli applied during the relative refractory period evoked significantly larger nerve volleys and thus activated larger numbers of dorsal column nerve fibres, indicating that the shortening of the refractory period was combined with an increase in the excitability of the dorsal column fibres. The DC‐evoked shortening of the refractory period might accordingly, as the DC‐evoked increase of the excitability of dorsal column fibres (see Jankowska & Hammar, 2021; Li et al, 2020), be linked to their branching regions.…”

“…The most marked differences between fibres stimulated within and outside the dorsal columns will probably lie in the morphology of afferent fibres at their branching sites, as the denuded areas of the axons at the sites where axon collaterals are issued are much larger than the nodes of Ranvier in peripheral nerves (see Jankowska & Hammar, 2021; Lucas‐Osma et al, 2018; Nicol & Walmsley, 1991). These differences in morphology may be combined with differences in membrane properties and the voltage‐gated and other ion channels, but the features of the branching regions of dorsal column fibres have only recently become the focus of investigation (Hari et al, 2021; Lucas‐Osma et al, 2018).…”

“…The effects of epidural polarisation (1 μA for 1 min) were tested both on the excitability and the refractory period of dorsal column fibres (Figure 1a). Changes in the excitability were defined as described previously, using nerve volleys evoked by near-threshold stimuli (20-30 μA) (for references, see Jankowska & Hammar, 2021). The degree of excitability was established during a 5 min control period and subsequently during 1 min of cathodal DC application followed by a 15 min post-polarisation period.…”

“…Previous studies have revealed a considerable degree of both short‐ and long‐term plasticity in nerve fibre properties (for recent references, see Bucher & Goaillard, 2011; Debanne, 2004; Debanne et al, 2011; Jankowska & Hammar, 2021; Suminaite et al, 2019). Our own interest has been in the long‐lasting increase in the excitability of afferent nerve fibres providing input to the spinal cord following their short‐lasting epidural direct current (DC) polarisation (Bączyk & Jankowska, 2018; Jankowska et al, 2017; Li et al, 2020) which might enhance effects of clinical rehabilitation procedures combined with spinal polarisation.…”

“…It will also be shown that the refractory period of afferent fibres traversing the dorsal columns is nearly half of that of fibres in either peripheral nerves or in the dorsal roots and is modulated to a much greater extent. These specific properties of the dorsal column fibres relate the long‐lasting effects of DC on the refractoriness to those on the excitability of afferent fibres traversing the dorsal columns and thereby to their branching regions (for references, see Jankowska & Hammar, 2021; Li et al, 2020).…”