This study was performed to examine the hypothesis that thalamic-projecting neurons of mesopontine cholinergic nuclei display activity patterns that are compatible with their role in inducing and maintaining activation processes in thalamocortical systems during the states of waking (W) and rapid-eye-movement (REM) sleep associated with desynchronization of the electroencephalogram (EEG). A sample of 780 neurons located in the peribrachial (PB) area of the pedunculopontine tegmental nucleus and in the laterodorsal tegmental (LDT) nucleus were recorded extracellularly in unanesthetized, chronically implanted cats. Of those neurons, 82 were antidromically invaded from medial, intralaminar, and lateral thalamic nuclei: 570 were orthodromically driven at short latencies from various thalamic sites: and 45 of the latter elements are also part of the 82 cell group, as they were activated both antidromically and synaptically from the thalamus. There were no statistically significant differences between firing rates in the PB and LDT neuronal samples. Rate analyses in 2 distinct groups of PB/LDT neurons, with fast (greater than 10 Hz) and slow (less than 2 Hz) discharge rates in W, indicated that (1) the fast-discharging cell group had higher firing rates in W and REM sleep compared to EEG-synchronized sleep (S), the differences between all states being significant (p less than 0.0005); (2) the slow-discharging cell group increased firing rates from W to S and further to REM sleep, with significant difference between W and S (p less than 0.01), as well as between W or S and REM sleep (p less than 0.0005). Interspike interval histograms of PB and LDT neurons showed that 75% of them have tonic firing patterns, with virtually no high-frequency spike bursts in any state of the wake-sleep cycle. We found 22 PB cells that discharged rhythmic spike trains with recurring periods of 0.8-1 sec. Autocorrelograms revealed that this oscillatory behavior disappeared when their firing rate increased during REM sleep. Dynamic analyses of sequential firing rates throughout the waking-sleep cycle showed that none of the full-blown states of vigilance is associated with a uniform level of spontaneous firing rate. Signs of decreased discharge frequencies of mesopontine neurons appeared toward the end of quiet W, preceding by about 10-20 sec the most precocious signs of EEG synchronization heralding the sleep onset. During transition from S to W, rates of spontaneous discharges increased 20 sec before the onset of EEG desynchronization.(ABSTRACT TRUNCATED AT 400 WORDS)

Previous investigations in various motor and sensory cortical areas have shown that fast oscillations Hz)'of focal electroencephalogram and multiunit activities occur spontaneously during increased alertness or are dependent upon optimal sensory stimuli. We now report the presence of 20-to 40-Hz rhythmic activities in intracellularly recorded thalamocortical cells of the cat. In some neurons, subthreshold oscillations were triggered by depolarizing pulses and eventually gave rise to action potentials. In other neurons, the oscillations consisted of fast prepotentials, occasionally generating full spikes that arose from the resting or even from hyperpolarized membrane potential levels, and leading to trains of spikes at more depolarized levels. The rhythmic nature ofthese fast prepotgntials was confimed by means of an autocorrelation study, which demonstrated clear peaks at 25-ms intervals (40 Hz). In-view of the recent evidence that mesopontine cholinergic nuclei trigger and maintain activation processes in thalamocortical systems, we tested the possibility that stimulation of these brainstem nuclei potentiates the 40-Hz waves on the background of the cortical electroencephalogram. 4396The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

A slow (0.5-4 Hz) oscillation of thalamic neurons was recently described and attributed to the interplay of two intrinsic currents. In this study, we investigated the network modulation of this intrinsic thalamic oscillation within the frequency range of EEG sleep delta-waves. We performed intracellular and extracellular recordings of antidromically identified thalamocortical cells (n = 305) in sensory, motor, associational, and intralaminar nuclei of anesthetized cats. At the resting membrane potential, Vm (-60.3 +/- 0.4 mV, mean +/- SE), cortical stimulation induced spindle-like oscillations (7-14 Hz), whereas at Vm more negative than -65 mV the same stimuli triggered an oscillation within the EEG delta-frequency (0.5-4 Hz), consisting of low-threshold spikes (LTSs) followed by after hyperpolarizing potentials (AHPs). The LTS-AHP sequences outlasted cortical stimuli as a self-sustained rhythmicity at 1-2 Hz. Corticothalamic stimuli were able to transform subthreshold slow (0.5-4 Hz) oscillations, occurring spontaneously at Vm more negative than -65 mV, into rhythmic LTSs crowned by bursts of Na+ spikes that persisted for 10-20 sec after cessation of cortical volleys. Cortical volleys also revived a hyperpolarization-activated slow oscillation when it dampened after a few cycles. Auto- and crosscorrelograms of neuronal pairs revealed that unrelated cells became synchronized after a series of corticothalamic stimuli, with both neurons displaying rhythmic (1-2 Hz) bursts or spike trains. Since delta-thalamic oscillations, prevailing during late sleep stages, are triggered at more negative Vm than spindles characterizing the early sleep stage, we postulate a progressive hyperpolarization of thalamocortical neurons with the deepening of the behavioral state of EEG-synchronized sleep. In view of the evidence that cortical-elicited slow oscillations depend on synaptically induced hyperpolarization of thalamocortical cells, we propose that the potentiating influence of the corticothalamic input results from the engagement of two GABAergic thalamic cell classes, reticular and local-circuit neurons. The thalamocorticothalamic loop would transfer the spike bursts of thalamic oscillating cells to cortical targets, which in turn would reinforce the oscillation by direct pathways and/or indirect projections relayed by reticular and local-circuit thalamic cells. Stimulation of mesopontine cholinergic [peribrachial (PB) and laterodorsal tegmental (LDT)] nuclei in monoamine-depleted animals had an effect that was opposite to that exerted by corticothalamic volleys. PB/LDT stimulation reduced or suppressed the slow (1-4 Hz) oscillatory bursts of high-frequency spikes in thalamic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

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The only mesopontine neurons previously described as involved in the transfer of ponto-geniculo-occipital (PGO) waves from the brain stem to the thalamus were termed PGO-on bursting cells. We have studied, in chronically implanted cats, neuronal activities in brain-stem peribrachial (PB) and laterodorsal tegmental (LDT) cholinergic nuclei in relation to PGO waves recorded from the lateral geniculate (LG) thalamic nucleus during rapid-eye-movement (REM) sleep. We constructed peri-PGO histograms of PB/LDT cells' discharges and analyzed the interspike interval distribution during the period of increased neuronal activity related to PGO waves. Six categories of PGO-related PB/LDT neurons with identified thalamic projections were found: 4 classes of PGO-on cells: PGO-off but REM-on cells: and post-PGO cells. The physiological characteristics of a given cell class were stable even during prolonged recordings. One of these cell classes (1) represents the previously described PGO-on bursting neurons, while the other five (2-6) are newly discovered neuronal types. (1) Some neurons (16% of PGO-related cells) discharged stereotyped low-frequency (120-180 Hz) spike bursts preceding the negative peak of the LG-PGO waves by 20-40 msec. These neurons had low firing rates (0.5-3.5 Hz) during all states. (2) A distinct cell class (22% of PGO-related neurons) fired high-frequency spike bursts (greater than 500 Hz) about 20-40 msec prior to the thalamic PGO wave. These bursts were preceded by a period (150-200 msec) of discharge acceleration on a background of tonically increased activity during REM sleep. (3) PGO-on tonic neurons (20% of PGO-related neurons) discharged trains of repetitive single spikes preceding the thalamic PGO waves by 100-150 msec, but never fired high-frequency spike bursts. (4) Other PGO-on neurons (10% of PGO-related neurons) discharged single spikes preceding thalamic PGO waves by 15-30 msec. On the basis of parallel intracellular recordings in acutely prepared, reserpine-treated animals, we concluded that the PGO-on single spikes arise from conventional excitatory postsynaptic potentials and do not reflect tiny postinhibitory rebounds. (5) A peculiar cellular class, termed PGO-off elements (8% of PGO-related neurons), consisted of neurons with tonic, high discharge rates (greater than 30 Hz) during REM sleep. These neurons stopped firing 100-200 msec before and during the thalamic PGO waves. (6) Finally, other neurons discharged spike bursts or tonic spike trains 100-300 msec after the initially negative peak of the thalamic PGO field potential (post-PGO elements, 23% of PGO-related neurons).(ABSTRACT TRUNCATED AT 400 WORDS)

1. The electrophysiological properties of neurones of the reticular thalamic (RE) nucleus were studied in acutely prepared cats under urethane anaesthesia. 2. Two main types of neuronal firing were recorded. At the resting membrane potential (-60 to -65 mV) tonic repetitive firing was elicited when the cell was activated synaptically or by current injection. From membrane potentials more negative than -75 mV, synaptic or direct stimulation generated a burst of action potentials. 3. The burst of RE cells consisted of a discharge of four to eight spikes riding on a slowly growing and decaying depolarization. The discharge rate during the burst showed a characteristic increase, followed by a decrease in frequency. 4. The burst response behaved as a graded phenomenon, as its magnitude was modulated by changing the intensity of the synaptic volley or the intensity of the injected current. 5. Spike-like small potentials presumably of dendritic origin occurred spontaneously and were triggered by synaptic or direct stimulation. They were all-or-none, voltage-dependent events. We postulate that these spikes originate in several hot spots in the dendritic arbor, with no reciprocal refractoriness and may generate multi-component depolarizations at the somatic level. 6. Excitatory postsynaptic potentials (EPSPs) evoked by internal capsule stimulation consisted of two components, the late one being blocked by hyperpolarization. Such compound EPSPs were followed by a period of decreased excitability during which a second response was diminished in amplitude. 7. A series of depolarizing waves at the frequency range of spindle oscillations was triggered by internal capsule stimulation. The individual depolarizing waves constituting the spindle oscillation gradually decreased in amplitude when decreasing the intensity of the stimulation. 8. These results, showing that RE cells are endowed with an excitable dendritic tree and a graded bursting behaviour, support the proposed role of RE nucleus as the generator and synchronizer of spindle rhythmicity.

SUMMARY1. Electrophysiologically identified thalamocortical neurones have been intraand extracellularly recorded in acutely prepared cats, under different anaesthetic conditions. 2. A slow (0 5-4 Hz) membrane potential oscillation was observed in thalamocortical cells recorded in motor, sensory, associational and intralaminar thalamic nuclei. The oscillation consisted of rhythmic low-threshold spikes alternating with after-hyperpolarizations.3. About 80 % of the neurones with intact cortical connections were set into the slow oscillatory mode by bringing their membrane potential to between -68 and -90 mV. The oscillation did not depend upon the occurrence of fast action potentials and did not outlast the imposed hyperpolarization.4. Anatomical or functional disconnection from related cortical areas resulted in a membrane potential hyperpolarization of about 9 mV and in the occurrence of spontaneous slow oscillations in virtually all recorded neurones. The intrinsic nature of the phenomenon was supported by the lack of rhythmic postsynaptic potentials as the cells were prevented from oscillating by outward current injection.5. In contrast with other thalamic nuclei, the slow oscillation has not been observed in anterior thalamic neurones despite their having similar basic electrophysiological properties.6. Barbiturate administration suppressed the slow oscillatory mode, an effect accompanied by a decrease in the membrane input resistance.7. Multiunit recordings of spontaneously oscillating cells showed epochs characterized by phase-related firing. This synchronous discharge was paralleled by a clear-cut build-up of field potentials in the frequency range of electroencephalogram slow or delta waves.8. These results demonstrate that the majority of thalamocortical neurones are endowed with electrophysiological properties allowing them to oscillate at 0 5-4 Hz, if they have a membrane potential more negative than -65 mV and a high input resistance. Such a condition is physiologically achieved in the deepest stages of electroencephalogram-synchronized sleep, as a result of brain stem-thalamic as well

1. Two types of cat reticular (RE) thalamic cells were disclosed by means of intracellular recordings under urethan anesthesia. The RE neurons were identified by their typical depolarizing spindle oscillations in response to synchronous stimulation of the internal capsule. 2. In type I neurons (n = 41), depolarizing current pulses induced tonic firing at the resting or slightly depolarized membrane potential (Vm) and triggered high-frequency spike bursts at a Vm more negative than -75 mV. As well, these cells discharged rebound bursts at the break of a hyperpolarizing current pulse. Internal capsule stimulation elicited spindle sequences made off by depolarizing waves giving rise to spike bursts. 3. Type II cells (n = 9) did not discharge spike bursts to large depolarizing current pulses even when the Vm reached -100 mV, nor did they fire rebound bursts after long-lasting hyperpolarizing current pulses or spike bursts riding on the rhythmic depolarizing components of spindle sequences. 4. Compared with type I cells, type II cells showed less frequency accommodation during tonic firing. The latter neuronal class discharged at high frequencies (40 Hz) with slight DC depolarization, approximately 8-10 Hz at the resting Vm, and no underlying synaptic or subthreshold oscillatory events could be detected when the firing was blocked by DC hyperpolarization. 5. The presence of two cell classes in the RE nucleus challenges the common view that this nucleus consists of a single neuronal class. We suggest that a different set of conductances is present in type II RE neurons, thus preventing the low-threshold Ca2+ current from dominating the behavior of these cells.