Network modulation of a slow intrinsic oscillation of cat thalamocortical neurons implicated in sleep delta waves: Cortically induced synchronization and brainstem cholinergic suppression

Abstract

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 δ-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, V(m) (-60.3 ± 0.4 mV, mean ± SE), cortical stimulation induced spindle-like oscillations (7-14 Hz), whereas at V(m) more negative than -65 mV the same stimuli triggered an oscillation within the EEG δ-frequency (0.5-4 Hz), consisting of low-threshold spikes (LTSs) followed by afterhyperpolarizing 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 V(m) 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 δ-thalamic oscillations, prevailing during late sleep stages, are triggered at more negative V(m) 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. The PB/LDT effect was associated with depolarization of thalamocortical neurons and EEG activation. The cortical EEG response included the appearance of 40 Hz cortical waves. The short-lasting effect of PB/LDT stimulation lasted for 2-3 sec, was accompanied by increased membrane conductance, and was blocked by the nicotinic antagonist mecamylamine. Less often, the PB/LDT-induced disruption of the slow oscillation lasted for 10-15 sec. Similarly to the effect exerted by PB/LDT stimulation, the slow oscillation of bursting neurons recorded from the dorsal lateral geniculate neurons was suppressed and replaced by tonic firing as a result of photic stimulation. Our results demonstrate that diffusely projecting modulatory systems or sensory-specific channels that succeed in depolarizing target thalamic cells decouple synchronized neurons, disrupt the slow oscillation, and prepare thalamocortical cells to transfer incoming signals. These data indicate that, while the slow oscillation of individual thalamic neurons results from the interplay of their intrinsic currents, the synchronization of neuronal ensembles and, as a consequence, the genesis of macroscopic rhythmic EEG potentials, depend on the properties of thalamocortical networks including inhibitory thalamic cells. The suppression of δ-oscillation with transition from slow-wave sleep to either arousal or rapid-eye-movement sleep is largely due to brainstem-thalamic cholinergic modulation acting diffusely on thalamocortical systems.