Ephaptic Interactions in the Mammalian Olfactory System

Abstract

Ephaptic coupling refers to interactions between neurons mediated by current flow through the extracellular space. Ephaptic interactions between axons are considered negligible, because of the relatively large extracellular space and the layers of myelin that separate most axons. By contrast, olfactory nerve axons are unmyelinated and arranged in tightly packed bundles, features that may enhance ephaptic coupling. We tested the hypothesis that ephaptic interactions occur in the mammalian olfactory nerve with the use of a computational approach. Numerical solutions of models of axon fascicles show that significant ephaptic interactions occur for a range of physiologically relevant parameters. An action potential in a single axon can evoke action potentials in all other axons in the fascicle. Ephaptic interactions can also lead to synchronized firing of independently stimulated axons. Our findings suggest that ephaptic interactions may be significant determinants of the olfactory code and that such interactions may occur in other, similarly organized axonal or dendritic bundles.

Intensity coding in two-dimensional excitable neural networks

“…Indeed, the model relies more generally on lateral excitation, and could in principle even forego gap junctions specifically. In the olfactory nerve, for instance, it could be implemented via the electrical coupling mediated by ephaptic interactions among neighboring axons, which have recently been modeled by Bokil et al [17]. Neuronal circuits where mutual bidirectional excitation by chemical synapses occur could also be subjected to a similar modeling.…”

Intercellular interactions in the mammalian olfactory nerve

“…The concentration of ion channels and other multi-helix membrane proteins in a relatively small space between axons could facilitate ephaptic interactions (Bokil et al, 2001), spreading calcium waves (Cinelli and Salzberg, 1992), potassium ion fluxes (Bliss and Rosenberg, 1979), current oscillations (Stopfer et al, 1997), and paracrine communication. The extracellular material we observed between axons (Fig.…”

“…Intracellular messengers would be active only in individual axons; paracrine interactions, facilitated by the distribution of the large proteins along the small extracellular spaces, would affect only axons in close proximity; ephaptic interactions (Bokil et al, 2001) would extend through-out a small fascicle; and calcium waves and current oscillations could extend throughout large areas of the nerve layer. With regard to the last, the extensive gap junctions between ensheathing cells could effectively make them a functional unit, together able to contact a large proportion of the axons and therefore able to coordinate widespread changes in neuronal excitability.…”

“…We have argued (Bokil et al, 2001) that ephaptic interactions, as well as interneuronal interactions mediated by extruded potassium ions (Bliss and Rosenberg, 1979) First, olfactory receptors of mature mammals are constantly regenerated (Graziadei and Graziadei, 1979;Graziadei and Monti Graziadei, 1983), and developing neurons of the central nervous system are often extensively coupled by gap junctions (reviewed in Kandler and Katz, 1995;Naus and Bani-Yaghoub, 1998;Chang and Balice-Gordon, 2000). Second, olfactory receptor neurons express connexins, the proteins that form gap junctions.…”

Neuronal network analyses: premises, promises and uncertainties

“…First, there is the issue of ephaptic communication mediated by local chemical or electrical fields (Krnjevic 1986;Jefferys 1995;Bokil et al 2001;Kamermans & Fahrenfort 2004). These effects were assumed to have modest influences under physiological conditions (although significant roles were assumed in pathology), but activity-dependent changes in local electrical and ionic fields caused by changes in extracellular K þ and Ca 2þ are known to significantly affect cellular and synaptic function (Erulkar & Weight 1977;Borst & Sakmann 1999;Bokil et al 2001;Rusakov & Fine 2003;see Durand et al (2010) for a discussion of these effects). These interactions will be influenced by the structural arrangement of network neurons and synapses as well as the tortuosity and anisotropy of the extracellular space (which represents approx.…”