Ephaptic coupling

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Ephaptic coupling is a form of communication within the nervous system and is distinct from direct communication systems like electrical synapses and chemical synapses. It may refer to the coupling of adjacent (touching) nerve fibers caused by the exchange of ions between the cells, or it may refer to coupling of nerve fibers as a result of local electric fields.[1] In either case ephaptic coupling can influence the synchronization and timing of action potential firing in neurons. Myelination is thought to inhibit ephaptic interactions.[2]

History and etymology[edit]

The idea that the electrical activity generated by nervous tissue may influence the activity of surrounding nervous tissue is one that dates back to the late 19th century. Early experiments, like those by du Bois-Reymond,[3] demonstrated that the firing of a primary nerve may induce the firing of an adjacent secondary nerve (termed "secondary excitation"). This effect was not quantitatively explored, however, until experiments by Katz and Schmitt[4] in 1940, when the two explored the electric interaction of two adjacent limb nerves of the crab Carcinus maenas. Their work demonstrated that the progression of the action potential in the active axon caused excitability changes in the inactive axon. These changes were attributed to the local currents that form the action potential. For example, the currents that caused the depolarization (excitation) of the active nerve caused a corresponding hyperpolarization (depression) of the adjacent resting fiber. Similarly, the currents that caused repolarization of the active nerve caused slight depolarization in the resting fiber. Katz and Schmitt also observed that stimulation of both nerves could cause interference effects. Simultaneous action potential firing caused interference and resulted in decreased conduction velocity, while slightly offset stimulation resulted in synchronization of the two impulses.

In 1941 Arvanitaki[5] explored the same topic and proposed the usage of the term "ephapse" (from the Greek ephapsis and meaning "to touch") to describe this phenomenon and distinguish it from synaptic transmission. Over time the term ephaptic coupling has come to be used not only in cases of electric interaction between adjacent elements, but also more generally to describe the effects induced by any field changes along the cell membrane.[6]

Mechanism and effects[edit]

Role in excitation and inhibition[edit]

The early work performed by Katz and Schmitt demonstrated that ephaptic coupling between the two adjacent nerves was insufficient to stimulate an action potential in the resting nerve. Under ideal conditions the maximum depolarization observed was approximately 20% of the threshold stimulus.[4] This effect is the result of the exchange of ions between the two fibers. As the action potential wave propagates along the active axon it draws from ion stores in the resting axon and the characteristic influx and efflux of ions in the action potential are experienced in reverse by the resting axon. The resting axon experiences hyperpolarization, depolarization, and then a smaller hyperpolarization in contrast to the active axon's progression from depolarization to repolarization, and return to resting potential.

Role in synchronization and timing[edit]

Studies of ephaptic coupling have also focused on its role in the synchronization and timing of action potentials in neurons. In the simpler case of adjacent fibers that experience simultaneous stimulation the impulse is slowed because both fibers are limited to exchange ions solely with the interstitial fluid (increasing the resistance of the nerve). Slightly offset impulses (conduction velocities differing by less than 10%) are able to exchange ions constructively and the action potentials propagate slightly out of phase at the same velocity.

More recent research, however, has focused on the more general case of electric fields that affect a variety of neurons. It has been observed that local field potentials in cortical neurons can serve to synchronize neuronal activity.[7] Although the mechanism is unknown, it is hypothesized that neurons are ephaptically coupled to the frequencies of the local field potential. This coupling may effectively synchronize neurons into periods of enhanced excitability (or depression) and allow for specific patterns of action potential timing (often referred to as spike timing). This effect has been demonstrated and modeled in a variety of cases.[8][9]

A hypothesis or explanation behind the mechanism is "one-way", "master-slave", or "unidirectional synchronization" effect as mathematical and fundamental property of non-linear dynamic systems (oscillators like neurons) to synchronize under certain criteria. Such phenomenon was proposed and predicted to be possible between two HR neurons, since 2010 in simulations and modeling work by Hrg.[10] It was also shown that such unidirectional synchronization or copy/paste transfer of neural dynamics from master to slave(s) neurons, could be exhibited in different ways. Hence the phenomenon is of not only fundamental interest but also applied one from treating epilepsy to novel learning systems. Synchronization of neurons is in principle unwanted behavior, as brain would have zero information or be simply a bulb if all neurons would synchronize. Hence it is a hypothesis that neurobiology and evolution of brain coped with ways of preventing such synchronous behavior on large scale, using it rather in other special cases.


Ephaptic coupling in rat Purkinje cells of the cerebellum[edit]

One of the few known cases of a functional system in which ephaptic coupling is responsible for an observable physiological event is in the Purkinje cells of the rat cerebellum.[11] It was demonstrated in this study that the basket cells which encapsulate some regions of Purkinje fibers can cause inhibitory effects on the Purkinje cells. The firing of these basket cells, which occurs more rapidly than in the Purkinje cells, draws current across the Purkinje cell and generates a passive hyperpolarizing potential which inhibits the activity of the Purkinje cell. Although the exact functional role of this inhibition is still unclear, it may well have a synchronizing effect in the Purkinje cells as the ephaptic effect will limit the firing time.

A similar ephaptic effect has been studied in the Mauthner cells of teleosts.[12]

See also[edit]


  1. ^ Aur D., Jog, MS. (2010) Neuroelectrodynamics: Understanding the brain language, IOS Press, doi:10.3233/978-1-60750-473-3-i
  2. ^ Hartline, Daniel K. (2008). "What is myelin?.". Neuron Glia Biology. 4: 153163. doi:10.1017/S1740925X09990263. 
  3. ^ Biedermann, Wilhelm, Electro-physiology, 2, p. 270  (Google Books)
  4. ^ a b Bernhard Katz; Otto H. Schmitt (February 14, 1940), "Electric Interaction Between Two Adjacent Nerve Fibers", J Physiol, 97 (4): 471–488, doi:10.1113/jphysiol.1940.sp003823 
  5. ^ Arvanitaki (March 1, 1942), "Effects Evoked in an Axon by the Activity of a Contiguous One", J Neurophysiol, 5 (2): 89–108 
  6. ^ J. G. R. Jefferys (1995), "Nonsynaptic modulation of neuronal activity in the brain: Electric currents and extracellular ions", Physiol. Rev. 75: 689–723 
  7. ^ Anastassiou, C. A.; Perin, R.; Markram, H.; Koch, C. (2011). "Ephaptic coupling of cortical neurons". Nature Neuroscience. 14 (2): 217–23. doi:10.1038/nn.2727. PMID 21240273.  (direct link to full text)
  8. ^ Radman, T., Su, Y., An, J.H., Parra, L.C. & Bikson, M. (2007), "Spike timing amplifies the effect of electric fields on neurons: implications for endogenous field effects.", J. Neurosci., 27: 3030–3036, doi:10.1523/jneurosci.0095-07.2007, PMID 17360926 
  9. ^ Anastassiou, C.A., Montgomery, S.M., Barahona, M., Buzsáki, G. & Koch, C. (2010), "The effect of spatially inhomogeneous extracellular electric fields on neurons.", J. Neurosci., 30: 1925–1936, doi:10.1523/jneurosci.3635-09.2010, PMID 20130201 
  10. ^ Hrg, D. (2013), "Synchronization of two Hindmarsh–Rose neurons with unidirectional coupling.", Neural Networks, 40: 73–79, doi:10.1016/j.neunet.2012.12.010 
  11. ^ Korn, Henri; Axelrad, Herbert, "Electrical inhibition of Purkinje cells in the cerebellum of the rat", Proc. Natl. Acad. Sci. USA, 77 (10): 6244–6247, doi:10.1073/pnas.77.10.6244 
  12. ^ Faber, DS; Korn, H, "Electrical field effects: Their relevance in central neural networks", Physiological Reviews, 69: 821–863