title: Low-amplitude oscillations in the inferior olive: a model based on electrical coupling of neurons with heterogeneous channel densities.
abstract: The mechanism underlying subthreshold oscillations in inferior olivary cells is not known. To study this question, we developed a single-compartment, two-variable, Hodgkin-Huxley-like model for inferior olive neurons. The model consists of a leakage current and a low-threshold calcium current, whose kinetics were experimentally measured in slices. Depending on the maximal calcium and leak conductances, we found that a neuron model's response to current injection could be of four qualitatively different types: always stable, spontaneously oscillating, oscillating with injection of current, and bistable with injection of current. By the use of phase plane techniques, numerical integration, and bifurcation analysis, we subdivided the two-parameter space of channel densities into four regions corresponding to these behavioral types. We further developed, with the use of such techniques, an empirical rule of thumb that characterizes whether two cells when coupled electrically can generate sustained, synchronized oscillations like those observed in inferior olivary cells in slices, of low amplitude (0.1-10 mV) in the frequency range 4-10 Hz. We found that it is not necessary for either cell to be a spontaneous oscillator to obtain a sustained oscillation. On the other hand, two spontaneous oscillators always form an oscillating network when electrically coupled with any arbitrary coupling conductance. In the case of an oscillating pair of electrically coupled nonidentical cells, the coupling current varies periodically and is nonzero even for very large coupling values. The coupling current acts as an equalizing current to reconcile the differences between the two cells' ionic currents. It transiently depolarizes one cell and/or hyperpolarizes the other cell to obtain the regenerative response(s) required for the synchronized oscillation. We suggest that the subthreshold oscillations observed in the inferior olive can emerge from the electrical coupling between neurons with different channel densities, even if the inferior olive nucleus contains no or just a small proportion of spontaneously oscillating neurons.
authors.affiliation: Neurobiology Department, Hebrew University, Jerusalem, Israel.
authors.forename: Y
authors.initials: Y
authors.lastname: Manor
authors.forename: J
authors.initials: J
authors.lastname: Rinzel
authors.forename: I
authors.initials: I
authors.lastname: Segev
authors.forename: Y
authors.initials: Y
authors.lastname: Yarom
mesh_terms: D000818:Animals; D001931:Brain Mapping; D046508:Culture Techniques; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009847:Olivary Nucleus / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology*; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D007473:Ion Channels