Neuronal coupling by endogenous electric fields: cable theory and applications to coincidence detector neurons in the auditory brain stem

The ongoing activity of neurons generates a spatially and time-varying field of extracellular voltage (V-e). This V-e field reflects population-level neural activity, but does it modulate neural dynamics and the function of neural circuits? We provide a cable theory framework to study how a bundle of model neurons generates V-e and how this V-e feeds back and influences membrane potential (V-m). We find that these ephaptic interactions are small but not negligible. The model neural population can generate V-e with millivolt-scale amplitude, and this V-e perturbs the V-m of nearby cables and effectively increases their electrotonic length. After using passive cable theory to systematically study ephaptic coupling, we explore a test case: the medial superior olive (MSO) in the auditory brain stem. The MSO is a possible locus of ephaptic interactions: sounds evoke large (millivolt scale) V-e in vivo in this nucleus. The V-e response is thought to be generated by MSO neurons that perform a known neuronal computation with submillisecond temporal precision (coincidence detection to encode sound source location). Using a biophysically based model of MSO neurons, we find millivolt-scale ephaptic interactions consistent with the passive cable theory results. These subtle membrane potential perturbations induce changes in spike initiation threshold, spike time synchrony, and time difference sensitivity. These results suggest that ephaptic coupling may influence MSO function.