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SUMMARY1. The oscillatory properties ofthe membrane potential in inferior olivary neurones were studied in guinea-pig brain-stem slices maintained in vitro.2. Intracellular double-ramp current injection at frequencies of 1-20 Hz revealed that inferior olivary neurones tend to fire at two preferred frequencies: 3-6 Hz when the cells were actively depolarized (resting potential less than -50 mV), and 9-12 Hz when they were actively hyperpolarized (resting potential more than -75 mV).3. In 10 % of the experiments spontaneous subthreshold oscillations of the membrane potential were observed. These oscillations, which resembled sinusoidal wave forms and had a frequency of 4-6 Hz and an amplitude of 5-10 mV, occurred synchronously in all cells tested within the slice. 4. These oscillations persisted in the presence of 10-4 M-tetrodotoxin and were blocked by Ca2+ conductance blockers or by the removal of Ca2+ from the bathing solution. The oscillations were affected by gross extracellular stimulation of the slice but not by intracellular activation of any given neurone. The data indicate that these oscillations reflect the properties of neuronal ensembles comprised of a large number of coupled elements.5. Similar ensemble oscillation could be induced, in most experiments, by adding harmaline (0-1 mg/ml) and serotonin (10-4 M) to the bath and could be blocked by bath addition of noradrenaline. Harmaline was found to increase cell excitability by hyperpolarizing the neurones and shifting the inactivation curve for the somatic Ca2+ spike to a more positive membrane potential level.6. The role inferior olivary oscillations play in the organization of motor coordination is discussed.

SUMMARYThe electrophysiological properties of guinea-pig inferior olivary (I.o.) cells have been studied in an in vitro brain stem slice preparation.1. Intracellular recordings from 185 neurones in this nucleus reveal that antidromic, orthodromic or direct stimulation generates action potentials consisting ofa fast spike followed by an after-depolarizing potential (ADP). The ADP had an amplitude of 49 + 8 mV (mean + S.D.) and a duration which varied over a wide range with the level of depolarization. This ADP is followed by an after-hyperpolarizing potential (AHP) having an amplitude of 12 + 3 mV (mean + S.D.) from rest and lasting up to 250 msec. The AHP shows a rebound depolarization wave.2. Synaptic activation may be obtained by peri-olivary stimulation with a bipolar electrode located in the immediate vicinity of the i.o. nucleus. These potentials are a mixture of depolarizing and hyperpolarizing synaptic events which can be reversed by direct membrane polarization.3. Addition of tetrodotoxin (TTX) to the bath, or removal of extracellular Na, abolishes the fast initial action potential but does not modify the ADP or the AHP. Blockage of Ca conductance by Co, Mn, Cd or D600, or replacement of Ca by Mg, abolishes the ADP-AHP sequence.4. Hyperpolarization ofthe neurone uncovers a low-threshold Ca conductance which is inactivated at rest and has similar pharmacological properties to the ADP. This low-threshold spike plays a central role in the rebound potential following the AHP.

1. Intracellular recordings were made from neurons in slices from guinea-pig frontal cortex. In 50 % of the cells, sustained subthreshold voltage oscillations were evoked by long (> 6 s) depolarizing pulses. The peak-to-peak amplitude of these oscillations was less than 5 mV and the frequency was voltage dependent, increasing with depolarization from 4 (near rest) to 20 Hz (at 30 mV depolarization). 2. The impedance-frequency relationship of both oscillating and non-oscillating cells was studied by intracellular injection of sinusoidal current with linearly changing frequency. In most cells, a peak in the impedance magnitude (resonant behaviour) was observed at depolarized levels. The frequency of the peak impedance (peak frequency) increased with depolarization from 3 (near rest) to 15 Hz (at 30 mV depolarization).3. Application of TTX (10-6 M) significantly decreased the impedance magnitude near the peak frequency. The subthreshold oscillations, however, as well as the action potentials, were fully blocked by TTX. On the other hand, TEA (15 mM) and Cs+ (5 mM) abolished both the subthreshold oscillations and the resonant behaviour. Replacing Ca21 with Co2+ (5 mM) or Ni2+ (1 mM) did not abolish the subthreshold oscillations. The peak in the frequency-response curve was only slightly reduced. 4. An isopotential membrane model, consisting of a leak current, a fast persistent sodium current, a slow non-inactivating potassium current (with the kinetics of the M-current) and membrane capacitance, is sufficient to produce both voltage oscillations and resonant behaviour. The kinetics of the K+ current by itself is sufficient to produce resonance behaviour. The Na+ current amplifies the peak impedance magnitude and is essential for the generation of subthreshold oscillation. The model correctly predicted the behaviour of the frequency response before and after TTX and TEA application, as well as the relation between the expected passive impedance and the experimental impedance. 5. We speculate that the tendency of the neurons to generate voltage signals at a certain frequency (as a result of the subthreshold oscillations) and to preferentially respond to inputs arriving at the same frequency (the resonance behaviour) promotes population activity at that preferred frequency.

A persistent change in neuronal activity after brief stimuli is a common feature of many neuronal microcircuits. This persistent activity can be sustained by ongoing reverberant network activity or by the intrinsic biophysical properties of individual cells. Here we demonstrate that rat and guinea pig cerebellar Purkinje cells in vivo show bistability of membrane potential and spike output on the time scale of seconds. The transition between membrane potential states can be bidirectionally triggered by the same brief current pulses. We also show that sensory activation of the climbing fiber input can switch Purkinje cells between the two states. The intrinsic nature of Purkinje cell bistability and its control by sensory input can be explained by a simple biophysical model. Purkinje cell bistability may have a key role in the short-term processing and storage of sensory information in the cerebellar cortex.