D Contreras

Spatiotemporal analysis of local field potentials and unit discharges in cat cerebral cortex during natural wake and sleep states.

The electroencephalogram displays various oscillation patterns during wake and sleep states, but their spatiotemporal distribution is not completely known. Local field potentials (LFPs) and multiunits were recorded simultaneously in the cerebral cortex (areas 5–7) of naturally sleeping and awake cats. Slow-wave sleep (SWS) was characterized by oscillations in the slow (<1 Hz) and delta (1–4 Hz) frequency range. The high-amplitude slow-wave complexes consisted in a positivity of depth LFP, associated with neuronal silence, followed by a sharp LFP negativity, correlated with an increase of firing. This pattern was of remarkable spatiotemporal coherence, because silences and increased firing occurred simultaneously in units recorded within a 7 mm distance in the cortex. During wake and rapid-eye-movement (REM) sleep, single units fired tonically, whereas LFPs displayed low-amplitude fast activities with increased power in fast frequencies (15–75 Hz). In contrast with the widespread synchronization during SWS, fast oscillations during REM and wake periods were synchronized only within neighboring electrodes and small time windows (100–500 msec). This local synchrony occurred in an apparent irregular manner, both spatially and temporally. Brief periods (<1 sec) of fast oscillations were also present during SWS in between slow-wave complexes. During these brief periods, the spatial and temporal coherence, as well as the relation between units and LFPs, was identical to that of fast oscillations of wake or REM sleep. These results show that natural SWS in cats is characterized by slow-wave complexes, synchronized over large cortical territories, interleaved with brief periods of fast oscillations, characterized by local synchrony, and of characteristics similar to that of the sustained fast oscillations of activated states.

Control of spatiotemporal coherence of a thalamic oscillation by corticothalamic feedback.

The mammalian thalamus is the gateway to the cortex for most sensory modalities. Nearly all thalamic nuclei also receive massive feedback projections from the cortical region to which they project. In this study, the spatiotemporal properties of synchronized thalamic spindle oscillations (7 to 14 hertz) were investigated in barbiturate-anesthetized cats, before and after removal of the cortex. After complete ipsilateral decortication, the long-range synchronization of thalamic spindles in the intact cortex hemisphere changed into disorganized patterns with low spatiotemporal coherence. Local thalamic synchrony was still present, as demonstrated by dual intracellular recordings from nearby neurons. In the cortex, synchrony was insensitive to the disruption of horizontal intracortical connections. These results indicate that the global coherence of thalamic oscillations is determined by corticothalamic projections.

Electrophysiological properties of intralaminar thalamocortical cells discharging rhythmic (≈40 HZ) spike-bursts at ≈1000 HZ during waking and rapid eye movement sleep

Abstract Thalamocortical neurons located in the large-celled district of the cat intralaminar centrolateral nucleus were found to discharge spike-bursts with unusually high frequencies (800–1000 Hz) during spindle oscillations of the electroencephalogram. In chronically implanted animals, similar spike-bursts were also fired during wakefulness and rapid eye movement sleep, two behavioral states in which other thalamocortical neurons tonically fire single spikes. Such high-frequency spike-bursts recurred with a fast rhythm of 20–40 Hz during waking and rapid eye movement sleep. Intracellular recordings under barbiturate anesthesia showed that, during spindle oscillations, the spike-bursts of intralaminar neurons are generated by brief low-threshold spikes with a much shorter refractory phase than in other thalamocortical cells. Depolarizing pulses from the resting membrane

Cortically-induced coherence of a thalamic-generated oscillation.

Oscillatory patterns in neocortical electrical activity show various degrees of large-scale synchrony depending on experimental conditions, but the exact mechanisms underlying these variations of coherence are not known. Analysis of multisite local field potentials revealed that the coherence of spindle oscillations varied during different states. During natural sleep, the coherence was remarkably high over cortical distances of several millimeters, but could be disrupted by artificial cortical depression, similar to the effect of barbiturates. Possible mechanisms for these variations of coherence were investigated by computational models of interacting cortical and thalamic neurons, including their intrinsic firing patterns and various synaptic receptors present in the circuitry. The model indicates that modulation of the excitability of the cortex can affect spatiotemporal coherence with no change in the thalamus. The highest level of coherence was obtained by enhancing the excitability of cortical pyramidal cells, simulating the action of neuromodulators such as acetylcholine and noradrenaline. The underlying mechanism was due to cortex-thalamus-cortex loops in which a more excitable cortical network generated a more powerful and coherent feedback onto the thalamus, resulting in highly coherent oscillations, similar to the properties measured during natural sleep. In conclusion, these experiments and models are compatible with a powerful role for the cortex in triggering and synchronizing oscillations generated in the thalamus, through corticothalamic feedback projections. The model suggests that intracortical mechanisms may be responsible for synchronizing oscillations over cortical distances of several millimeters through cortex-thalamus-cortex loops, thus providing a possible cellular mechanism to explain the genesis of large-scale coherent oscillations in the thalamocortical system.

Synchronization of low-frequency rhythms in corticothalamic networks.

We have investigated the degree of synchronization between cortical, thalamic reticular and thalamocortical neurons of cats during low-frequency (< 15 Hz) sleep-like oscillations, as they appear under anaesthesia. We have also studied the effects exerted by cortical stimulation on the synchronization among thalamic units. Parallel experiments [Steriade et al. (1996) J. Neurosci. 16, 392-417] in this laboratory have demonstrated the similarity between the slow oscillation (< 1 Hz) under ketamine-xylazine anaesthesia and that occurring during the natural state of resting sleep. Spontaneous activity was recorded simultaneously, with independent microelectrodes, from groups of two to five physiologically identified neurons. The rhythmicity of spontaneous activity and the temporal relations between cellular discharges were statistically evaluated by auto- and crosscorrelation techniques. We have found no topography in the distribution of synchronization between thalamic reticular and thalamocortical cells. Only the slow, cortical-generated oscillation (< 1 Hz) displayed a stable frequency and correlation among groups of cortical and thalamic cells. The other two sleep oscillations (thalamic-generated spindles at 7-14 Hz and clock-like delta at 1-4 Hz) fluctuated in frequency and the degree of correlation between neurons varied. Cortical volleys entrained and synchronized thalamic cells, and triggered synchronized spindling in the thalamus. These results extend for large populations of cortical and thalamic neurons the phase relations found in intracellular recordings.

State-dependent fluctuations of low-frequency rhythms in corticothalamic networks.

We have studied the variations in the degree of correlated firing within the low-frequency sleep rhythms (< 15 Hz) between cortical, thalamic reticular and thalamocortical neurons during changes in the amplitude and frequency of brain electrical activity in anaesthetized cats. Extracellular discharges of neuronal groups of two to five physiologically identified cortical and thalamic units were recorded simultaneously with independent microelectrodes. The firing patterns and the temporal correlation between spike-trains were evaluated by auto- and crosscorrelograms. Although the animals were under deep anaesthesia, additional doses of the same or different anaesthetics were able to alter the electroencephalographic pattern, inducing waves with higher amplitude. Similar transitions occurred spontaneously. We found that the presence of rhythmic behaviour in cells of corticothalamic networks, as well as their degree of correlated firing, was extremely sensitive to even slight alterations in the state of the electroencephalogram. Cells belonging to the same functional system, but located distantly, became highly synchronized upon the increased amplitude of brain waves. Thus, an electroencephalogram characterized by slow waves corresponds to a state of rhythmic and correlated firing among cortical and thalamic neurons. The highly coherent activity during sleep patterns transcends the borders which limit the functioning during the waking brain.