Synchronized Oscillations in the Inferior Olive are Controlled by the
Hyperpolarization-Activated Cation Current Ih.
Thierry Bal and David A. McCormick.
Section of Neurobiology, Yale University School of Medicine, 333 Cedar
Street, New Haven, Connecticut 06473, david.mccormick@yale.edu, (203) 785-
4577, FAX (203) 785-5263, Inst. Alfred Fessard, CNRS, Ave de la Terrasse, Gif
sur Yvette, Cedex 91198, France, bal@bobby.iaf.cnrs-gif.fr.
APStracts 4:0058N, 1997.
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 (I.O.) of
the guinea pig and ferret was investigated in slices maintained in vitro.
Intracellular recordings in guinea pig or ferret I.O. neurons revealed that
these cells could generate sustained endogenous oscillations (4-10 Hz) at
hyperpolarized membrane potentials (-60 to -67 mV) following 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. In
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, indicated that a
Ca2+-activated K+ current makes a strong contribution to its generation.
However, even in the presence of apamin, hyperpolarization of I.O. 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 the hyperpolarization-
activated cation current, Ih, also contributes to the generation of the
afterhyperpolarization. Extracellular application of low concentrations of
cesium resulted in hyperpolarization of the membrane potential of I.O. neurons
and spontaneous 5-6 Hz oscillations in single, as well as networks, of I.O.
neurons. Application of larger concentrations of cesium reduced the frequency
of oscillation to 2-3 Hz or blocked the oscillation entirely. Based upon these
results, and those of Yarom and Llin s (1987), we propose that Ih contributes
to single and ensemble oscillations in the I.O. in two ways: 1) Ih contributes
to the determination of the resting membrane potential such that reduction of
Ih 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) Ih contributes to the generation of the
afterhyperpolarization and the "pacemaker" potential in between low threshold
Ca2+ spikes.
Received 15 November 1996; accepted in final form 4 February 1997.
APS Manuscript Number J898-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 20 February 1997