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===Role in excitation and inhibition===
===Role in excitation and inhibition===
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 potential|threshold stimulus]].<ref name="Katz"/> 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.
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 potential|threshold stimulus]].<ref name="Katz"/> However, conditions can be manipulated in such a way that the action potential from one neuron can be spread to a neighboring neuron. This was accomplished in one study in two experimental conditions: increased calcium concentrations, which lowered the threshold potential, or by submerging the axons in mineral oil, which increased resistance. While these manipulations do not reflect normal conditions, they do highlight the mechanisms behind ephaptic excitation. <ref name="Ramon"></ref>

Ephaptic coupling has also been found to play an important role in inhibition of neighboring neurons. Depending on the location and identity of the neurons, various mechanisms have been found to underlie ephaptic inhibition. In one study, newly excited neighboring neurons interfered with already sustained currents, thus lowering the extracellular potential and depolarizing the neuron in relation to its surrounding environment, effectively inhibiting the action potential's propagation. <ref name="van Naters"></ref>


===Role in synchronization and timing===
===Role in synchronization and timing===
Line 20: Line 22:
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.<ref>{{citation |author=Hrg, D. |title= Synchronization of two Hindmarsh–Rose neurons with unidirectional coupling.| journal=Neural Networks |volume=40 |pages=73–79 |year=2013 |doi=10.1016/j.neunet.2012.12.010}}</ref> 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.
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.<ref>{{citation |author=Hrg, D. |title= Synchronization of two Hindmarsh–Rose neurons with unidirectional coupling.| journal=Neural Networks |volume=40 |pages=73–79 |year=2013 |doi=10.1016/j.neunet.2012.12.010}}</ref> 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.


== Example ==
== Examples ==


===Cardiac tissue===
⚫
===Ephaptic coupling in rat Purkinje cells of the cerebellum===

The [[electrical conduction system of the heart]] has been robustly established. However, newer research has been challenging some of the previously accepted models. The role of ephaptic coupling in cardiac cells is becoming more apparent. One author even goes so far as to say, “While previously viewed as a possible alternative to electrotonic coupling, ephaptic coupling has since come to be viewed as operating in tandem with gap junctions, helping sustain conduction when gap junctional coupling is compromised.” <ref name="Veeraraghavan"></ref> Ephaptic interactions among cardiac cells help fill in the gaps that electrical synapses alone cannot account for. There are also a number of mathematical models that more recently incorporate ephaptic coupling into predictions about electrical conductance in the heart. <ref name="Lin"></ref>

===Epilepsy and seizures===

[[Epileptic seizure]]s occur when there is synchrony of electrical waves in the brain. Knowing the role that ephaptic coupling plays in maintaining synchrony in electrical signals, it makes sense to look for ephaptic mechanisms in this type of pathology. One study suggested that cortical cells represent an ideal place to observe ephaptic coupling due to the tight packing of axons, which allows for interactions between their electrical fields. They tested the effects of changing extracellular space (which affects local electrical fields) and found that one can block epileptic synchronization independent of chemical synapse manipulation simply by increasing the space between cells. <ref name="Dudek"></ref> Later, a model was created to predict this phenomenon and showed scenarios with greater extracellular spacing that effectively blocked epileptic synchronization in the brain. <ref name="Stacey"></ref>

===Olfactory system in the brain===

Neurons in the olfactory system are unmyelinated and densely packed and thus the often small effects of ephaptic coupling are more easily seen. A number of studies have shown how inhibition among neurons in the olfactory system work to fine tune integration of signals in response to odor. This inhibition has been shown to occur from changes in electrical potentials alone. <ref name="van Nater"></ref> The addition of ephaptic coupling to olfactory neuron models adds further support to the "dedicated-line" model in which each olfactory receptor sends its signal to one neuron. The inhibition due to ephaptic coupling would help account for the integration of signals that gives rise to more nuanced perception of smells. <ref name="Bokil"></ref>

==Mathematical models==

Due to the very small electrical fields produced by neurons, mathematical models are often used in order to test a number of manipulations. [[Cable theory]] is one of the most important mathematical equations in neuroscience. <ref name="Bedard"></ref> It calculates electrical current using capacitance and resistance as variables and has been the main basis for many predictions about ephaptic coupling in neurons. However, many authors have worked to create more refined models in order to more accurately represent the environments of the nervous system. For example, many authors have proposed models for cardiac tissue that includes additional variables that account for the unique structure and geometry of cardiac cells <ref name="Lin"></ref>, varying scales of size <ref name="Hand"></ref>, or three-dimensional electrodiffusion. <ref name="Mori"></ref>

==Animal models==

===Giant squid axons===

In 1978, basic tests were being conducted on giant squid neurons in order to find evidence of ephaptic events. It was shown that an action potential of one axon could be propagated to a neighboring axon. The level of transmission varied, from subthreshold changes to initiation of an action potential in a neighboring cell, but in all cases, it was apparent that there are implications of ephaptic coupling that are of physiological importance. <ref name="Ramon"></ref>

===Rat spinal cord and medulla===

One study tested the effects of ephaptic coupling by using both neurotransmitter anatagonists to block chemical synapses and gap junction blockers to block electrical synapses. It was found that rhythmic electrical discharge associated with fetal neurons in the rat spinal cord and medulla was still sustained. This suggests that connections between the neurons still exist and work to spread signals even without traditional synapses. These findings support a model in which ephaptic coupling works along side canonical synapses to propagate signals across neuronal networks. <ref name="Ren"></ref>

⚫
===Rat Purkinje cells of the cerebellum===


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 cell]]s of the rat cerebellum.<ref>{{citation |author1=Korn, Henri |author2=Axelrad, Herbert|title= Electrical inhibition of Purkinje cells in the cerebellum of the rat |journal=Proc. Natl. Acad. Sci. USA |volume=77 |issue=10 |pages=6244–6247 |doi=10.1073/pnas.77.10.6244}}</ref> It was demonstrated in this study that the [[basket cell]]s 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.
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 cell]]s of the rat cerebellum.<ref>{{citation |author1=Korn, Henri |author2=Axelrad, Herbert|title= Electrical inhibition of Purkinje cells in the cerebellum of the rat |journal=Proc. Natl. Acad. Sci. USA |volume=77 |issue=10 |pages=6244–6247 |doi=10.1073/pnas.77.10.6244}}</ref> It was demonstrated in this study that the [[basket cell]]s 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 cell]]s of [[Teleostei|teleosts]].<ref>{{citation |author1=Faber, DS |author2=Korn, H |title= Electrical field effects: Their relevance in central neural networks |journal=Physiological Reviews |volume=69 |pages=821–863}}</ref>
A similar ephaptic effect has been studied in the [[Mauthner cell]]s of [[Teleostei|teleosts]].<ref>{{citation |author1=Faber, DS |author2=Korn, H |title= Electrical field effects: Their relevance in central neural networks |journal=Physiological Reviews |volume=69 |pages=821–863}}</ref>

==Skepticism==

While the idea of non-synaptic interactions between neurons has existed since the 19th century, there has historically been a lot of skepticism in the field of neuroscience. Many people believed that the micro electrical fields produced by the neurons themselves were so small that they were negligible. <ref name="Bokil"></ref> While many supporters of the ephaptic coupling theory have been trying to prove its existence through experiments that block both chemical and electrical synapses, still some opponents in the field express caution. For example, in 2014, one scientist published a review that presents his skepticism on the idea of ephaptic coupling, saying “The agreement between their simulations and Poelzing’s data is impressive, but I will need a more definitive experimental confirmation before I can embrace the ephaptic hypothesis.” <ref name="Roth"></ref>He bases his caution in wanting more distinction between gap junctions' propagation of charge and true ephaptic coupling. Whether it is a true lack of evidence or simply obstinance in the face of change, many in the field are still not entirely convinced there is unambiguous evidence of ephaptic coupling.


== See also ==
== See also ==
Line 34: Line 66:
* [[Spike-field coherence]]
* [[Spike-field coherence]]
* [[NeuroElectroDynamics]]
* [[NeuroElectroDynamics]]
* [[Cable theory]]
* [[Local field potential]]


== References ==
== References ==
{{reflist|30em}}
{{reflist|30em}}
<ref name=”Ramon”>{{cite pmid|206154}}</ref>
<ref name=”Ren”>{{cite pmid|16148265}}</ref>
<ref name=”Bedard”>{{cite pmid|24032866}}</ref>
<ref name=”Veeraraghavan”>{{cite pmid|24414064}}</ref>
<ref name=”Hand”>{{cite pmid|20671202}}</ref>
<ref name=”Lin”>{{cite pmid|21078961}}</ref>
<ref name=”Mori”>{{cite pmid|18434544}}</ref>
<ref name=”Dudek”>{{cite journal |last=Dudek |first=F. Edward |last2=Yasumura |first2=Thomas |last3=Rash |first3=John E |year=1998 |title= Non-synaptic mechanisms in seizures and epileptogenesis |journal=Cell Biology International |volume=22 |issue=11/12 |pages=793-805 |publisher=Academic Press}}</ref>
<ref name=”Stacey”>{{cite pmid|25673735}}</ref>
<ref name=”Bokil”>{{cite pmid|11588203}}</ref>
<ref name=”van Naters”>{{cite pmid|24167484}}</ref>
<ref name=”Roth”>{{cite pmid|24559978}}</ref>


{{DEFAULTSORT:Ephaptic Coupling}}
{{DEFAULTSORT:Ephaptic Coupling}}

Revision as of 20:12, 16 April 2017

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

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

Role in excitation and inhibition

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] However, conditions can be manipulated in such a way that the action potential from one neuron can be spread to a neighboring neuron. This was accomplished in one study in two experimental conditions: increased calcium concentrations, which lowered the threshold potential, or by submerging the axons in mineral oil, which increased resistance. While these manipulations do not reflect normal conditions, they do highlight the mechanisms behind ephaptic excitation. [7]

Ephaptic coupling has also been found to play an important role in inhibition of neighboring neurons. Depending on the location and identity of the neurons, various mechanisms have been found to underlie ephaptic inhibition. In one study, newly excited neighboring neurons interfered with already sustained currents, thus lowering the extracellular potential and depolarizing the neuron in relation to its surrounding environment, effectively inhibiting the action potential's propagation. [8]

Role in synchronization and timing

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.[9] 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.[10][11]

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.[12] 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.

Examples

Cardiac tissue

The electrical conduction system of the heart has been robustly established. However, newer research has been challenging some of the previously accepted models. The role of ephaptic coupling in cardiac cells is becoming more apparent. One author even goes so far as to say, “While previously viewed as a possible alternative to electrotonic coupling, ephaptic coupling has since come to be viewed as operating in tandem with gap junctions, helping sustain conduction when gap junctional coupling is compromised.” [13] Ephaptic interactions among cardiac cells help fill in the gaps that electrical synapses alone cannot account for. There are also a number of mathematical models that more recently incorporate ephaptic coupling into predictions about electrical conductance in the heart. [14]

Epilepsy and seizures

Epileptic seizures occur when there is synchrony of electrical waves in the brain. Knowing the role that ephaptic coupling plays in maintaining synchrony in electrical signals, it makes sense to look for ephaptic mechanisms in this type of pathology. One study suggested that cortical cells represent an ideal place to observe ephaptic coupling due to the tight packing of axons, which allows for interactions between their electrical fields. They tested the effects of changing extracellular space (which affects local electrical fields) and found that one can block epileptic synchronization independent of chemical synapse manipulation simply by increasing the space between cells. [15] Later, a model was created to predict this phenomenon and showed scenarios with greater extracellular spacing that effectively blocked epileptic synchronization in the brain. [16]

Olfactory system in the brain

Neurons in the olfactory system are unmyelinated and densely packed and thus the often small effects of ephaptic coupling are more easily seen. A number of studies have shown how inhibition among neurons in the olfactory system work to fine tune integration of signals in response to odor. This inhibition has been shown to occur from changes in electrical potentials alone. [17] The addition of ephaptic coupling to olfactory neuron models adds further support to the "dedicated-line" model in which each olfactory receptor sends its signal to one neuron. The inhibition due to ephaptic coupling would help account for the integration of signals that gives rise to more nuanced perception of smells. [18]

Mathematical models

Due to the very small electrical fields produced by neurons, mathematical models are often used in order to test a number of manipulations. Cable theory is one of the most important mathematical equations in neuroscience. [19] It calculates electrical current using capacitance and resistance as variables and has been the main basis for many predictions about ephaptic coupling in neurons. However, many authors have worked to create more refined models in order to more accurately represent the environments of the nervous system. For example, many authors have proposed models for cardiac tissue that includes additional variables that account for the unique structure and geometry of cardiac cells [14], varying scales of size [20], or three-dimensional electrodiffusion. [21]

Animal models

Giant squid axons

In 1978, basic tests were being conducted on giant squid neurons in order to find evidence of ephaptic events. It was shown that an action potential of one axon could be propagated to a neighboring axon. The level of transmission varied, from subthreshold changes to initiation of an action potential in a neighboring cell, but in all cases, it was apparent that there are implications of ephaptic coupling that are of physiological importance. [7]

Rat spinal cord and medulla

One study tested the effects of ephaptic coupling by using both neurotransmitter anatagonists to block chemical synapses and gap junction blockers to block electrical synapses. It was found that rhythmic electrical discharge associated with fetal neurons in the rat spinal cord and medulla was still sustained. This suggests that connections between the neurons still exist and work to spread signals even without traditional synapses. These findings support a model in which ephaptic coupling works along side canonical synapses to propagate signals across neuronal networks. [22]

Rat Purkinje cells of the cerebellum

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.[23] 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.[24]

Skepticism

While the idea of non-synaptic interactions between neurons has existed since the 19th century, there has historically been a lot of skepticism in the field of neuroscience. Many people believed that the micro electrical fields produced by the neurons themselves were so small that they were negligible. [18] While many supporters of the ephaptic coupling theory have been trying to prove its existence through experiments that block both chemical and electrical synapses, still some opponents in the field express caution. For example, in 2014, one scientist published a review that presents his skepticism on the idea of ephaptic coupling, saying “The agreement between their simulations and Poelzing’s data is impressive, but I will need a more definitive experimental confirmation before I can embrace the ephaptic hypothesis.” [25]He bases his caution in wanting more distinction between gap junctions' propagation of charge and true ephaptic coupling. Whether it is a true lack of evidence or simply obstinance in the face of change, many in the field are still not entirely convinced there is unambiguous evidence of ephaptic coupling.

See also

References

  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, vol. 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. ^ a b Cite error: The named reference Ramon was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference van Naters was invoked but never defined (see the help page).
  9. ^ 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)
  10. ^ 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{{citation}}: CS1 maint: multiple names: authors list (link)
  11. ^ 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{{citation}}: CS1 maint: multiple names: authors list (link)
  12. ^ 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
  13. ^ Cite error: The named reference Veeraraghavan was invoked but never defined (see the help page).
  14. ^ a b Cite error: The named reference Lin was invoked but never defined (see the help page).
  15. ^ Cite error: The named reference Dudek was invoked but never defined (see the help page).
  16. ^ Cite error: The named reference Stacey was invoked but never defined (see the help page).
  17. ^ Cite error: The named reference van Nater was invoked but never defined (see the help page).
  18. ^ a b Cite error: The named reference Bokil was invoked but never defined (see the help page).
  19. ^ Cite error: The named reference Bedard was invoked but never defined (see the help page).
  20. ^ Cite error: The named reference Hand was invoked but never defined (see the help page).
  21. ^ Cite error: The named reference Mori was invoked but never defined (see the help page).
  22. ^ Cite error: The named reference Ren was invoked but never defined (see the help page).
  23. ^ 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
  24. ^ Faber, DS; Korn, H, "Electrical field effects: Their relevance in central neural networks", Physiological Reviews, 69: 821–863
  25. ^ Cite error: The named reference Roth was invoked but never defined (see the help page).

[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]

  1. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 206154, please use {{cite journal}} with |pmid=206154 instead.
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  8. ^ Dudek, F. Edward; Yasumura, Thomas; Rash, John E (1998). "Non-synaptic mechanisms in seizures and epileptogenesis". Cell Biology International. 22 (11/12). Academic Press: 793–805.
  9. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 25673735, please use {{cite journal}} with |pmid=25673735 instead.
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