title: Synchronized oscillations in the inferior olive are controlled by the hyperpolarization-activated cation current I(h).
abstract: The participation of a hyperpolarization-activated cationic current in the generation of oscillations in single inferior olive neurons and in the generation of ensemble oscillations in the inferior olive nucleus (IO) of the guinea pig and ferret was investigated in slices maintained in vitro. Intracellular recordings in guinea pig or ferret 10 neurons revealed that these cells could generate sustained endogenous oscillations (4-10 Hz) at hyperpolarized membrane potentials (-60 to -67 mV) after the intracellular injection of a brief hyperpolarizing current pulse. These oscillations appeared as the rhythmic generation of a low-threshold Ca2+ spike that typically initiated one or two fast Na+-dependent action potentials. Between low-threshold Ca2+ spikes was an afterhyperpolarization that formed a "pacemaker" potential. Local application of apamin resulted in a large reduction in the amplitude of the afterhyperpolarization, indicating that a Ca2+-activated K+ current makes a strong contribution to its generation. However, even in the presence of apamin, hyperpolarization of IO neurons results in a "depolarizing sag" of the membrane potential that was blocked by local application of Cs+ or partial replacement of extracellular Na+ with choline+ or N-methyl-D-glucamine+, suggesting that I(h) also contributes to the generation of the afterhyperpolarization. Extracellular application of low concentrations of cesium resulted in hyperpolarization of the membrane potential of IO neurons and spontaneous 5- to 6-Hz oscillations in single, as well as networks, of IO neurons. Application of larger concentrations of cesium reduced the frequency of oscillation to 2-3 Hz or blocked the oscillation entirely. On the basis of these results, we propose that I(h) contributes to single and ensemble oscillations in the IO in two ways: 1) I(h) contributes to the determination of the resting membrane potential such that reduction of I(h) results in hyperpolarization of the membrane potential and an increased propensity of oscillation through removal of inactivation of the low-threshold Ca2+ current; and 2) I(h) contributes to the generation of the afterhyperpolarization and the pacemaker potential between low-threshold Ca2+ spikes.
authors.affiliation: Institut Alfred Fessard, Centre National de la Recherche Scientifique, Gif sur Yvette, France.
authors.forename: T
authors.initials: T
authors.lastname: Bal
authors.forename: D A
authors.initials: DA
authors.lastname: McCormick
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D015220:Calcium Channels / Q000502:physiology*; D005260:Female; D005289:Ferrets; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009847:Olivary Nucleus / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D015222:Sodium Channels