Ephaptic coupling

Abstract: There is now persuasive evidence that trigeminal neuralgia is usually caused by demyelination of trigeminal sensory fibres within either the nerve root or, less commonly, the brainstem. In most cases, the trigeminal nerve root demyelination involves the proximal, CNS part of the root and results from compression by an overlying artery or vein. Other causes of trigeminal neuralgia in which demyelination is involved or implicated include multiple sclerosis and, probably, compressive space-occupying masses in the posterior fossa. Examination of trigeminal nerve roots from patients with compression of the nerve root by an overlying blood vessel has revealed focal demyelination in the region of compression, with close apposition of demyelinated axons and an absence of intervening glial processes. Similar foci of nerve root demyelination and juxtaposition of axons have been demonstrated in multiple sclerosis patients with trigeminal neuralgia. Experimental studies indicate that this anatomical arrangement favours the ectopic generation of spontaneous nerve impulses and their ephaptic conduction to adjacent fibres, and that spontaneous nerve activity is likely to be increased by the deformity associated with pulsatile vascular indentation. Decompression of the nerve root produces rapid relief of symptoms in most patients with vessel-associated trigeminal neuralgia, probably because the resulting separation of demyelinated axons and their release from focal distortion reduce the spontaneous generation of impulses and prevent their ephaptic spread. The role of remyelination in initial symptomatic recovery after decompression is unclear. However, remyelination may help to ensure that relief of symptoms is sustained after decompression of the nerve root and may also be responsible for the spontaneous remission of the neuralgia in some patients. In addition to causing symptomatic relief, vascular decompression leads to rapid recovery of nerve conduction across the indented root, a phenomenon that, we suggest, is likely to reflect the reversal of compression-induced conduction block in larger myelinated fibres outside the region of demyelination. Trigeminal neuralgia can occur in association with a range of other syndromes involving vascular compression and hyperactivity of cranial nerves. Clinical observations and electrophysiological studies support the concept that demyelination and ephaptic spread of excitation underlie most, if not all, of these conditions.

Abstract: The electrochemical processes that underlie neural function manifest themselves in ceaseless spatiotemporal field fluctuations. However, extracellular fields feed back onto the electric potential across the neuronal membrane via ephaptic coupling, independent of synapses. The extent to which such ephaptic coupling alters the functioning of neurons under physiological conditions remains unclear. To address this question, we stimulated and recorded from rat cortical pyramidal neurons in slices with a 12-electrode setup. We found that extracellular fields induced ephaptically mediated changes in the somatic membrane potential that were less than 0.5 mV under subthreshold conditions. Despite their small size, these fields could strongly entrain action potentials, particularly for slow (<8 Hz) fluctuations of the extracellular field. Finally, we simultaneously measured from up to four patched neurons located proximally to each other. Our findings indicate that endogenous brain activity can causally affect neural function through field effects under physiological conditions.

Abstract: Ephaptic interactions between a neuron and axons or dendrites passing by its cell body can be, in principle, more significant than ephaptic interactions among axons in a fiber tract. Extracellular action potentials outside axons are small in amplitude and spatially spread out, while they are larger in amplitude and much more spatially confined near cell bodies. We estimated the extracellular potentials associated with an action potential in a cortical pyramidal cell using standard one-dimensional cable theory and volume conductor theory. Their spatial and temporal pattern reveal much about the location and timing of currents in the cell, especially in combination with a known morphology, and simple experiments could resolve questions about spike initiation. From the extracellular potential we compute the ephaptically induced polarization in a nearby passive cable. The magnitude of this induced voltage can be several mV, does not spread electrotonically, and depends only weakly on the passive properties of the cable. We discuss their possible functional relevance.