Ephaptic-Axonal Interactions Shape Radial Biases During Neural Self-Organization

Communication in the brain seems to not just be mediated by axonal action potential transmission resulting in post-synaptic modulations, but also by electrical field effects of depolarizing neurons, i.e. ephaptic coupling. The significant role of ephaptic coupling in synchronizing neural ensembles has been conjectured to indirectly affect ontogenetic neural circuit development through sub-threshold impacts on spike timing. We therefore hypothesized synchronously firing ensembles to emerge at spatial distances where ephaptic and axonal signals were most temporally correlated. To test our model of ephaptic-axonal interactions during neural self-organization, we compared its predictions to developmental outcomes of cortical rat tissue on high-density multielectrode arrays in vitro. We observed a cosinusoidal variation of synchronous activity over radial distances that can be understood to result from the joint effects of ephaptic and axonal signals during gamma-band bursts. Recurrent amplification of this theorized interaction effect during ontogenetic differentiation appears to radially bias the spectral profile of neural activity in the spatial distribution of neural ensembles. While long-term plasticity has been conventionally attributed to synaptic action alone, we show that that the interaction effects with ephaptic waves deserve further investigation.