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Biomedical subjects

M Steriade

Publications and source records attributed to M Steriade.

At least 37 records · Page 2Linked to original sources
PubMed2001

Active neocortical processes during quiescent sleep.

The neocortex and the thalamus constitute a unified oscillatory machine during different states of vigilance. The cortically generated slow sleep oscillation has the virtue of grouping other sleep rhythms, including those arising in the thalamus, within complex wave-sequences. Despite the coherent oscillatory activity in corticothalamic circuits, on the functional side there is dissociation between thalamus and neocortex during sleep. While dorsal thalamic neurons undergo inhibitory processes induced by prolonged spikebursts of GABAergic thalamic reticular neurons, the cortex displays, periodically, a rich spontaneous activity and preserves the capacity to process internally generated signals. Simultaneous intracellular recordings from thalamic and cortical neurons show that short-term plasticity processes occur after prolonged and rhythmic spike-bursts fired by thalamic and cortical neurons during slow-wave sleep oscillations. This may serve to support resonant phenomena and reorganize corticothalamic circuitry.

Action Potentials↗
PubMed2000

Neuronal and glial membrane potentials during sleep and paroxysmal oscillations in the neocortex.

This study investigated the fluctuations in the membrane potential of cortical neurons and glial cells during the slow sleep oscillation and spike-wave (SW) seizures. We performed dual neuron-glia intracellular recordings together with multisite field potential recordings from cortical suprasylvian association areas 5 and 7 of cats under ketamine-xylazine anesthesia. Electrical stimuli applied to the cortex elicited responses consisting of a biphasic depolarization in glial cells, which was associated with an EPSP-IPSP sequence in neurons. During the slow (<1 Hz) oscillation, extracellular measurements of the potassium concentration revealed periodic increases with an amplitude of 1-2 mm, similar in shape to glial activities. We suggest that, through their uptake mechanisms, glia cells modulate the neuronal excitability and contribute to the pacing of the slow oscillation. The slow oscillation often evolved into SW paroxysms, mimicking sleep-triggered seizures. This transition was associated with increased coupling between the depolarizing events in neurons and glial cells. During seizures, the glial membrane potential displayed phasic negative events related to the onset of the paroxysmal depolarizing shifts in neurons. These events were not voltage dependent and increased their incidence and amplitude with the development of the seizure. It is suggested that the intraglial transient negativities represent field reflections of synchronized neuronal potentials. We propose that the mechanisms underlying the neuron-glia communication include, besides the traditional neurotransmitter- and ion-mediated pathways, field effects crossing their membranes as a function of the state of the cortical network.

Activity Cycles↗
PubMed2000

Corticothalamic resonance, states of vigilance and mentation.

During various states of vigilance, brain oscillations are grouped together through reciprocal connections between the neocortex and thalamus. The coherent activity in corticothalamic networks, under the control of brainstem and forebrain modulatory systems, requires investigations in intact-brain animals. During behavioral states associated with brain disconnection from the external world, the large-scale synchronization of low-frequency oscillations is accompanied by the inhibition of synaptic transmission through thalamocortical neurons. Despite the coherent oscillatory activity, on the functional side there is dissociation between the thalamus and neocortex during slow-wave sleep. While dorsal thalamic neurons undergo inhibitory processes due to the prolonged spike-bursts of thalamic reticular neurons, the cortex displays, periodically, a rich spontaneous activity and preserves the capacity to process internally generated signals that dominate the state of sleep. In vivo experiments using simultaneous intracellular recordings from thalamic and cortical neurons show that short-term plasticity processes occur after prolonged and rhythmic spike-bursts fired by thalamic and cortical neurons during slow-wave sleep oscillations. This may serve to support resonant phenomena and reorganize corticothalamic circuitry, determine which synaptic modifications, formed during the waking state, are to be consolidated and generate a peculiar kind of dreaming mentation. In contrast to the long-range coherent oscillations that occur at low frequencies during slow-wave sleep, the sustained fast oscillations that characterize alert states are synchronized over restricted territories and are associated with discrete and differentiated patterns of conscious events.

Animals↗
PubMed2000

Changes in neuronal conductance during different components of cortically generated spike-wave seizures.

Neuronal conductance was studied in anesthetized cats during cortically generated spike-wave seizures arising from slow sleep oscillation. Single and dual intracellular recordings from neocortical neurons were used. The changes were similar whether the seizures occurred spontaneously, or were evoked by electrical stimulation or induced by bicuculline. In all seizures, the conductance increased from the very onset of the seizure and returned to control values only at the end of the postictal depression. Simultaneous intracellular recordings from two neurons showed that the neuron leading the other neuron displayed the largest increase in membrane conductance. The changes in neuronal conductance during the two phases of the slow sleep oscillation, i.e. highest during depolarizations and lowest during hyperpolarizations, were similar to those occurring during the "spike" and "wave" components of seizures. (1) Maximal conductance was found during the paroxysmal depolarizing shift corresponding to the electroencephalogram "spike" (median: 252 nS; range: 90 to more than 400 nS). It was highest at the onset of the depolarized plateau and decreased thereafter. (2) During the hyperpolarization corresponding to the electroencephalogram "wave", the conductance was significantly lower (median: 71 nS; range: 41 to 140 nS). (3) The conductance was elevated during the fast runs (median: 230 nS; range: 92 to 350 nS) which occurred in two-thirds of the seizures. (4) The conductance values during postictal depression were situated between those measured during the seizure hyperpolarizations and during sleep hyperpolarizations. The conductance decreased exponentially back to the values of the slow sleep oscillation over the total duration of the postictal depression. The data suggest that the major mechanism underlying the "wave"-related hyperpolarizing component of spike-wave seizures relies mainly not on active inhibition, but on a mixture of disfacilitation and potassium currents.

Action Potentials↗
PubMed2000

Origin of slow cortical oscillations in deafferented cortical slabs.

An in vivo preparation has been developed to study the mechanisms underlying spontaneous sleep oscillations. Dual and triple simultaneous intracellular recordings were made from neurons in small isolated cortical slabs (10 mm x 6 mm) in anesthetized cats. Spontaneously occurring slow sleep oscillations, present in the adjacent intact cortex, were absent in small slabs. However, the isolated slabs displayed brief active periods separated by long periods of silence, up to 60 s in duration. During these silent periods, 60% of neurons showed non-linear amplification of low-amplitude depolarizing activity. Nearly 40% of the cells, twice as many as in intact cortex, were classified as intrinsically bursting. In cortical network models based on Hodgkin-Huxley-like neurons, the summation of simulated spontaneous miniature excitatory postsynaptic potentials was sufficient to activate a persistent sodium current, initiating action potentials in single neurons that then spread through the network. Consistent with this model, enlarging the isolated cortical territory to an isolated gyrus (30 mm x 20 mm) increased the probability of initiating large-scale activity. In these larger territories, both the frequency and regularity of the slow oscillation approached that generated in intact cortex. The frequency of active periods in an analytical model of the cortical network accurately predicted the scaling observed in simulations and from recordings in cortical slabs of increasing size.

Animals↗
PubMed2000

Spiking-bursting activity in the thalamic reticular nucleus initiates sequences of spindle oscillations in thalamic networks.

Recent intracellular and local field potential recordings from thalamic reticular (RE) neurons in vivo as well as computational modeling of the isolated RE nucleus suggest that, at relatively hyperpolarized levels of membrane potentials, the inhibitory postsynaptic potentials (IPSPs) between RE cells can be reversed and gamma-aminobutyric acid-A (GABA(A)) -mediated depolarization can generate persistent spatio-temporal patterns in the RE nucleus. Here we investigate how this activity affects the spatio-temporal properties of spindle oscillations with computer models of interacting RE and thalamocortical (TC) cells. In a one-dimensional network of RE and TC cells, sequences of spindle oscillations alternated with localized patterns of spike-burst activity propagating inside the RE network. New sequences of spindle oscillations were initiated after removal of I(h)-mediated depolarization of the TC cells. The length of the interspindle lulls depended on the intrinsic and synaptic properties of RE and TC cells and was in the range of 3-20 s. In a two-dimensional model, GABA(A)-mediated 2-3 Hz oscillations persisted in the RE nucleus during interspindle lulls and initiated spindle sequences at many foci within the RE-TC network simultaneously. This model predicts that the intrinsic properties of the reticular thalamus may contribute to the synchrony of spindle oscillations observed in vivo.

Action Potentials↗
PubMed2000

Integration of low-frequency sleep oscillations in corticothalamic networks.

The corticothalamic system acts as a complex network in promoting the various oscillatory patterns (slow oscillation, spindles, delta) that characterize the state of quiet sleep. Local synchronizing mechanisms of any of the above-mentioned oscillations occur at the site of their genesis, thalamic or cortical. These mechanisms are assisted by the wide-range, synchronized occurrence of the cortical slow oscillation, which finally produces the coalesced picture of slow-wave sleep EEG. Multisite, simultaneous intracellular and field potential recordings in cat, as well as EEG recordings in human were performed in order to assess the state of synchrony and the propagation of various sleep rhythms in the corticothalamic network.

Animals↗
PubMed1999

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.

Animals↗
PubMed1999

Coherent oscillations and short-term plasticity in corticothalamic networks.

The neocortex and thalamus are a unified oscillatory machine. Different types of brain rhythms, which characterize various behavioral states, are combined within complex wave-sequences. During the stage of sleep that is associated with low-frequency and high-amplitude brain rhythms, the excitatory component of a cortically generated slow oscillation is effective in triggering thalamically generated rhythms and in increasing their spatiotemporal coherence over widespread territories. Thus, the study of coherent oscillations, as they appear naturally during states of vigilance in animals and humans, requires intact-brain preparations in which the neocortex and thalamus engage in a permanent dialog. Sleep oscillations are associated with rhythmic spike-bursts or spike-trains in thalamic and cortical neurons, which lead to persistent excitability changes consisting of increased depolarizing responses and decreased inhibitory responses. These short-term plasticity processes could be used to consolidate memory traces acquired during wakefulness, but can also lead to paroxysmal (hypersynchronous) episodes, similar to those observed in some epileptic seizures.

Animals↗
PubMed1999

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.

Anesthesia↗
PubMed1999

Self-sustained rhythmic activity in the thalamic reticular nucleus mediated by depolarizing GABAA receptor potentials.

Intracellular recordings from reticular thalamic (RE) neurons in vivo revealed inhibitory postsynaptic potentials (IPSPs) between RE cells that reversed and became depolarizing at the hyperpolarized membrane potentials that occur during sleep. These excitatory IPSPs can directly trigger low-threshold spikes (LTSs). The oscillatory mechanisms underlying IPSP-triggered LTSs crowned by spike bursts were investigated in models of isolated RE networks. In a one-dimensional network model, external stimulation evoked waves of excitation propagating at a constant velocity of 25-150 cells per second. In a large-scale, two-dimensional model of the reticular nucleus, the network showed transient or self-sustained oscillations controlled by the maximum conductance of the low-threshold calcium current and the membrane potential. This model predicts that the isolated reticular nucleus could initiate sequences of spindle oscillations in thalamocortical networks in vivo.

Action Potentials↗
PubMed1999

Intracellular study of excitability in the seizure-prone neocortex in vivo.

The excitability of neocortical neurons from cat association areas 5-7 was investigated during spontaneously occurring seizures with spike-wave (SW) complexes at 2-3 Hz. We tested the antidromic and orthodromic responsiveness of neocortical neurons during the "spike" and "wave" components of SW complexes, and we placed emphasis on the dynamics of excitability changes from sleeplike patterns to seizures. At the resting membrane potential, an overwhelming majority of neurons displayed seizures over a depolarizing envelope. Cortical as well as thalamic stimuli triggered isolated paroxysmal depolarizing shifts (PDSs) that eventually developed into SW seizures. PDSs could also be elicited by cortical or thalamic volleys during the wave-related hyperpolarization of neurons, but not during the spike-related depolarization. The latencies of evoked excitatory postsynaptic potentials (EPSPs) progressively decreased, and their slope and depolarization surface increased, from the control period preceding the seizure to the climax of paroxysm. Before the occurrence of full-blown seizures, thalamic stimuli evoked PDSs arising from the postinhibitory rebound excitation, whereas cortical stimuli triggered PDSs immediately after the early EPSP. These data shed light on the differential excitability of cortical neurons during the spike and wave components of SW seizures, and on the differential effects of cortical and thalamic volleys leading to such paroxysms. We conclude that the wave-related hyperpolarization does not represent GABA-mediated inhibitory postsynaptic potentials (IPSPs), and we suggest that it is a mixture of disfacilitation and Ca(2+)-dependent K(+) currents, similar to the prolonged hyperpolarization of the slow sleep oscillation.

Animals↗
PubMed1999

Spontaneous and artificial activation of neocortical seizures.

The aim of this study is to disclose the mechanisms underlying the recruitment of neocortical networks during slow-wave sleep oscillations evolving into spike-wave (SW) seizures. 1) We investigated the activation of SW seizures in a seizure-prone neocortex by means of electrical stimuli applied within the frequency range of spontaneous sleep oscillations. Stimuli were grouped in bursts of 10 Hz, similar to sleep spindles, and repeated every 2 s, to reproduce their rhythmic recurrence imposed by the slow (<1 Hz) sleep oscillation. Either cortical or thalamic stimuli, which were applied while the cortex displayed sleeplike activity, gradually induced paroxysmal responses in intracellularly recorded neocortical neurons, which were virtually identical to those of spontaneous seizures and consisted of a progressive buildup of paroxysmal depolarizing shifts (PDSs). 2) The ability of cortical networks to follow stimuli was tested at various stimulation frequencies (1-3 Hz) and quantified by calculating the entropy of the ensuing oscillation. Rhythmic PDSs were optimally induced, and the lowest entropy was generated, at a stimulation frequency around 1.5 Hz. Fast runs at 10-15 Hz, which often override PDSs, thus contributing to the polyspike-wave pattern of seizures, were induced by cortical stimuli, but were disturbed by thalamic stimuli. Spontaneous seizures generally evolved toward an accelerated discharge of PDSs. It is suggested that these accelerating trends during SW seizures act as protective mechanisms by provoking the uncoupling of cortical networks and eventually arresting the seizure.

Animals↗
PubMed1998

Leading role of thalamic over cortical neurons during postinhibitory rebound excitation.

The postinhibitory rebound excitation is an intrinsic property of thalamic and cortical neurons that is implicated in a variety of normal and abnormal operations of neuronal networks, such as slow or fast brain rhythms during different states of vigilance as well as seizures. We used dual simultaneous intracellular recordings of thalamocortical neurons from the ventrolateral nucleus and neurons from the motor cortex, together with thalamic and cortical field potentials, to investigate the temporal relations between thalamic and cortical events during the rebound excitation that follows prolonged periods of stimulus-induced inhibition. Invariably, the rebound spike-bursts in thalamocortical cells occurred before the rebound depolarization in cortical neurons and preceded the peak of the depth-negative, rebound field potential in cortical areas. Also, the inhibitory-rebound sequences were more pronounced and prolonged in cortical neurons when elicited by thalamic stimuli, compared with cortical stimuli. The role of thalamocortical loops in the rebound excitation of cortical neurons was shown further by the absence of rebound activity in isolated cortical slabs. However, whereas thalamocortical neurons remained hyperpolarized after rebound excitation, because of the prolonged spike-bursts in inhibitory thalamic reticular neurons, the rebound depolarization in cortical neurons was prolonged, suggesting the role of intracortical excitatory circuits in this sustained activity. The role of intrathalamic events in triggering rebound cortical activity should be taken into consideration when analyzing information processes at the cortical level; at each step, corticothalamic volleys can set into action thalamic inhibitory neurons, leading to rebound spike-bursts that are transferred back to the cortex, thus modifying cortical activities.

Animals↗
PubMed1998

Role of thalamic and cortical neurons in augmenting responses and self-sustained activity: dual intracellular recordings in vivo.

Progressively increasing (augmenting) responses are elicited in thalamocortical systems by repetitive stimuli at approximately 10 Hz. Repeated pulse trains at this frequency lead to a form of short-term plasticity consisting of a persistent increase in depolarizing synaptic responses as well as a prolonged decrease in inhibitory responses. In this study, we have investigated the role of thalamocortical (TC) and neocortical neurons in the initiation of thalamically and cortically evoked augmenting responses. Dual intracellular recordings in anesthetized cats show that thalamically evoked augmenting responses of neocortical neurons stem from a secondary depolarization (mean onset latency of 11 msec) that develops in association with a diminution of the early EPSP. Two nonexclusive mechanisms may underlie the increased secondary depolarization during augmentation: the rebound spike bursts initiated in simultaneously recorded TC cells, which precede by approximately 3 msec the onset of augmenting responses in cortical neurons; and low-threshold responses, uncovered by hyperpolarization in cortical neurons, which may follow EPSPs triggered by TC volleys. Thalamic stimulation proved to be more efficient than cortical stimulation at producing augmenting responses. Stronger augmenting responses in neocortical neurons were found in deeply located (<0.8 mm, layers V-VI) regular-spiking and fast rhythmic-bursting neurons than in superficial neurons. Although cortical augmenting responses are preceded by rebound spike bursts in TC cells, the duration of the self-sustained postaugmenting oscillatory activity in cortical neurons exceeds that observed in TC neurons. These results emphasize the role of interconnected TC and cortical neurons in the production of augmenting responses leading to short-term plasticity processes.

Animals↗
PubMed1998

Computational models of thalamocortical augmenting responses.

Repetitive stimulation of the dorsal thalamus at 7-14 Hz produces an increasing number of spikes at an increasing frequency in neocortical neurons during the first few stimuli. Possible mechanisms underlying these cortical augmenting responses were analyzed with a computer model that included populations of thalamocortical cells, thalamic reticular neurons, up to two layers of cortical pyramidal cells, and cortical inhibitory interneurons. Repetitive thalamic stimulation produced a low-threshold intrathalamic augmentation in the model based on the deinactivation of the low-threshold Ca2+ current in thalamocortical cells, which in turn induced cortical augmenting responses. In the cortical model, augmenting responses were more powerful in the "input" layer compared with those in the "output" layer. Cortical stimulation of the network model produced augmenting responses in cortical neurons in distant cortical areas through corticothalamocortical loops and low-threshold intrathalamic augmentation. Thalamic stimulation was more effective in eliciting augmenting responses than cortical stimulation. Intracortical inhibition had an important influence on the genesis of augmenting responses in cortical neurons: A shift in the balance between intracortical excitation and inhibition toward excitation transformed an augmenting responses to long-lasting paroxysmal discharge. The predictions of the model were compared with in vivo recordings from neurons in cortical area 4 and thalamic ventrolateral nucleus of anesthetized cats. The known intrinsic properties of thalamic cells and thalamocortical interconnections can account for the basic properties of cortical augmenting responses.

Animals↗
PubMed1998

Electrophysiological correlates of sleep delta waves.

Recent studies have disclosed several oscillations occurring during resting sleep within the frequency range of the classical delta band (0.5-4 Hz). There are at least 3 oscillations with distinct mechanisms and sites of origin: a slow (<1 Hz) cortically-generated oscillation, a clock-like thalamic oscillation (1-4 Hz), and a cortical oscillation (1-4 Hz). The present paper reviews data on these oscillations and the possible mechanisms which coalesce them into the polymorphic waves of slow wave sleep. Data stem from intracellular (over 500 single cell and 50 double impalements) and field potentials recorded from the cortex and thalamus of cats (120 animals) under ketamine and xylazine anesthesia. Other experiments were based on whole night EEG recordings from humans (5 subjects). The frequency of the slow oscillation both in anesthetized animals and in naturally sleeping humans ranged between 0.1 and 1 Hz (89% of the cases being between 0.5 and 0.9 Hz). The slow (<1 Hz) oscillation is reflected in the EEG as rhythmic sequences of surface-negative waves (associated with hyperpolarizations of deeply-lying neurons) and surface-positive K-complexes (representing excitation in large pools of cortical neurons). Through its long-range synchronization, the slow oscillation has the ability to trigger and to group thalamically-generated spindles and two delta (1-4 Hz) oscillations. Finally, it is argued that the analysis of the electroencephalogram should transcend the spectral analyses, by taking into account the shape of the waves and, when possible, the basic mechanisms that generate those waves.

Animals↗