SYNCHRONIZED OSCILLATIONS IN THE INFERIOR OLIVE ARE CONTROLLED BY THEHYPERPOLARIZATION-ACTIVATED CATION CURRENT I-H

The participation of a hyperpolarization-activated cationic current in the generation of oscillations in single inferior olive neurons and i n the generation of ensemble oscillations in the inferior olive nucleu s (IO) of the guinea pig and ferret was investigated in slices maintai ned in vitro. Intracellular recordings in guinea pig or ferret IO neur ons revealed that these cells could generate sustained endogenous osci llations (4-10 Hz) at hyperpolarized membrane potentials (-60 to -67 m V) after the intracellular injection of a brief hyperpolarizing curren t pulse. These oscillations appeared as the rhythmic generation of a l ow-threshold Ca2+ spike that typically initiated one or two fast Na+-d ependent action potentials. Between low-threshold Ca2+ spikes was an a fterhyperpolarization that formed a ''pacemaker'' potential. Local app lication of apamin resulted in a large reduction in the amplitude of t he afterhyperpolarization, indicating that a Ca2+-activated K+ current makes a strong contribution to its generation. However, even in the p resence of apamin, hyperpolarization of IO neurons results in a ''depo larizing sag'' of the membrane potential that was blocked by local app lication of Cs+ or partial replacement of extracellular Na+ with choli ne(+) or N-methyl-D-glucamine(+), suggesting that I-h also contributes to the generation of the afterhyperpolarization. Extracellular applic ation of low concentrations of cesium resulted in hyperpolarization of the membrane potential of IO neurons and spontaneous 5- to 6-Hz oscil lations in single, as well as networks, of IO neurons. Application of larger concentrations of cesium reduced the frequency of oscillation t o 2-3 Hz or blocked the oscillation entirely. On the basis of these re sults, we propose that I-h contributes to single and ensemble oscillat ions 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 propensit y of oscillation through removal of inactivation of the low-threshold Ca2+ current; and 2) I-h contributes to the generation of the afterhyp erpolarization and the pacemaker potential between low-threshold Ca2spikes.