Shortest Loops are Pacemakers in Random Networks of Electrically Coupled Axons

High-frequency oscillations (HFOs) are an important part of brain activity in health and disease. However, their origins remain obscure and controversial. One possible mechanism depends on the presence of sparsely distributed gap junctions that electrically couple the axons of principal cells. A plexus of electrically coupled axons is modeled as a random network with bi-directional connections between its nodes. Under certain conditions the network can demonstrate one of two types of oscillatory activity. Type I oscillations (100–200 Hz) are predicted to be caused by spontaneously spiking axons in a network with strong (high conductance) gap junctions. Type II oscillations (200–300 Hz) require no spontaneous spiking and relatively weak (low-conductance) gap junctions, across which spike propagation failures occur. The type II oscillations are reentrant and self-sustained. Here we examine what determines the frequency of type II oscillations. Using simulations we show that the distribution of loop lengths is the key factor for determining frequency in type II network oscillations. We first analyze spike failure between two electrically coupled cells using a model of anatomically reconstructed CA1 pyramidal neuron. Then network oscillations are studied by a cellular automaton model with random network connectivity, in which we control loop statistics. We show that oscillation periods can be predicted from the network’s loop statistics. The shortest loop, around which a spike can travel, is the most likely pacemaker candidate. The principle of one loop as a pacemaker is remarkable, because random networks contain a large number of loops juxtaposed and superimposed, and their number rapidly grows with network size. This principle allows us to predict the frequency of oscillations from network connectivity and visa versa. We finally propose that type I oscillations may correspond to ripples, while type II oscillations correspond to so-called fast ripples.