Rhythmogenesis in a hybrid system--interconnecting an olivary neuron to an analog network of coupled oscillators

A hybrid system in which an olivary neuron was interconnected to an analog simulator was used to study possible mechanisms by which the combined behavior of individual olivary neurons evokes synchronized membrane potential oscillations in a large population of neurons. The analog system was composed of four identical, interconnected oscillating units, each of which was capable of producing a damped sinusoidal oscillation in response to a trigger signal. When the units were coupled to each other, a single trigger pulse to one unit could evoke sustained oscillations. The integrity of the connections within the system was required to maintain these oscillations. In the hybrid system the analog system was reciprocally connected to an olivary neuron in a slice preparation. As in the analog system, the hybrid system could generate sustained oscillations following a trigger pulse to one of the units, as well as following a low threshold Ca spike in the neuron. Activation of the low threshold Ca conductance in the olivary neuron was necessary to achieve both gain and in-phase activity within the hybrid system, and thereby sustain the oscillations. The ability of the hybrid system to generate sustained oscillation is frequency dependent. Sustained oscillations were readily obtained at a "preferred frequency" of 5.2 Hz (n = 7) which was independent on the parameters used by the simulator, or on the membrane potential of the neurons. These results, which demonstrate the advantage of a new experimental approach developed to study rhythmogenesis in inferior olivary neurons, support the hypothesis that the inferior olivary nucleus, acting as an interconnected network of oscillating units, can generate an accurate subthreshold oscillation that serves as an internal time reference.