CHOLINERGIC AND NORADRENERGIC MODULATION OF THE SLOW (APPROXIMATE-TO-0.3 HZ) OSCILLATION IN NEOCORTICAL CELLS

1. The pedunculopontine tegmental (PPT) cholinergic nucleus and the lo cus coeruleus (LC) noradrenergic nucleus were electrically stimulated to investigate their effects on the recently described slow oscillatio n (almost-equal-to 0.3 Hz) of neocortical neurons. Intracellular recor dings of slowly oscillating, regular-spiking and intrinsically burstin g neurons from cortical association areas 5 and 7 (n = 140) were perfo rmed in anesthetized cats. 2. Pulse trains to the PPT nucleus produced the blockage of rhythmic (almost-equal-to 0.3 Hz) depolarizing-hyperp olarizing sequences in 79% of tested cortical neurons and transformed this slow cellular rhythm into tonic firing. The latency of the cortic al cellular response to PPT stimulation was 1.2 +/- 0.5 (SE) s and its duration was 15.9 +/- 1.9 s. The PPT-elicited suppression of the slow cellular oscillation was accompanied by an activation of the electroe ncephalogram (EEG) having a similar time course. Fast Fourier transfor m analyses of EEG activities before and after PPT stimulation showed t hat the PPT-evoked changes consisted of decreased power of slow rhythm s (0-8 Hz) and increased power of fast rhythms (24-33 Hz); these chang es were statistically significant. 3. The blockage of the slow cellula r oscillation was mainly achieved through the diminution or suppressio n of the long-lasting hyperpolarizations separating the rhythmic depol arizing envelopes. This effect was observed even when PPT pulse trains disrupted the oscillation without inducing overt depolarization and i ncreased firing rate. The durations of the prolonged hyperpolarization s were measured during a 40-s window (20 s before and 20 s after the P PT pulse train) and were found to decrease from 1.5 +/- 0.2 to 0.7 +/- 0.1 s. The values of the product resulting from the duration (in seco nds), the amplitude (in millivolts), and number of such hyperpolarizin g events within 20-s periods were 51.5 5 and 5.1 +/- 1.9 before and af ter PPT stimulation, respectively. 4. The PPT effect was suppressed by systemic administration of a muscarinic antagonist, scopolamine, but not by mecamylamine, a nicotinic antagonist. 5. The PPT effect on cell ular and EEG cortical slow oscillation survived, although its duration was reduced, in animals with kainate-induced lesions of thalamic nucl ei projecting to areas 5 and 7 (n = 3) as well as in animals with simi lar excitotoxic lesions leading to extensive neuronal loss in nucleus basalis (n = 2). These data indicate that the PPT effect is transmitte d to neocortex through either thalamic or basal forebrain relays. 6. L C stimulation induced the blockage of the slow cellular rhythm as well as an activated EEG response, similar to the PPT effect. The threshol d of the LC-induced response was usually higher than that of the PPT-e licited response. The LC effects were blocked after systemic administr ation of clonidine, an alpha2 agonist. 7. The blockage of the slow cor tical oscillation was also seen during short-lasting epochs of EEG act ivation occurring spontaneously. 8. We conclude that the disruption of the slow cortical oscillation mainly results from the suppression of the long-lasting hyperpolarizations and we suggest that this effect ma y be due, at least partially, to the cholinergic or noradrenergic bloc kage of Ca2+-dependent K+ currents.