Ephaptic coupling is a form of communication within the nervous system and is distinct from direct communication systems like electrical synapses and chemical synapses. The phrase 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. In either case ephaptic coupling can influence the synchronization and timing of action potential firing in neurons. Research suggests that myelination may inhibit ephaptic interactions.

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 Emil du Bois-Reymond, 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 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 Angélique Arvanitaki 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.

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. 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.

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.

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. 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.

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. It was also shown that such unidirectional synchronization or copy/paste transfer of neural dynamics from master to slave 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. A study in July 2023 found that mathematical models of ephaptic coupling predicted in vivo data of neural activity. The authors likened the electric field to a conductor of an orchestra and neurons to the musicians. Then the field,like the conductor, listens to the music and guides the musicians accordingly. In an opinion paper, they also suggested that not only neurons but other parts of the cytoskeleton generate electromagnetic fields that influence individual neurons, and called this cytoelectric coupling. 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.