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M Steriade

Publications and source records attributed to M Steriade.

At least 19 recordsLinked to original sources
PubMed2005

Grouping of brain rhythms in corticothalamic systems.

Different brain rhythms, with both low-frequency and fast-frequency, are grouped within complex wave-sequences. Instead of dissecting various frequency bands of the major oscillations that characterize the brain electrical activity during states of vigilance, it is conceptually more rewarding to analyze their coalescence, which is due to neuronal interactions in corticothalamic systems. This concept of unified brain rhythms does not only include low-frequency sleep oscillations but also fast (beta and gamma) activities that are not exclusively confined to brain-activated states, since they also occur during slow-wave sleep. The major factor behind this coalescence is the cortically generated slow oscillation that, through corticocortical and corticothalamic drives, is effective in grouping other brain rhythms. The experimental evidence for unified oscillations derived from simultaneous intracellular recordings of cortical and thalamic neurons in vivo, while recent studies in humans using global methods provided congruent results of grouping different types of slow and fast oscillatory activities. Far from being epiphenomena, spontaneous brain rhythms have an important role in synaptic plasticity. The role of slow-wave sleep oscillation in consolidating memory traces acquired during wakefulness is being explored in both experimental animals and human subjects. Highly synchronized sleep oscillations may develop into seizures that are generated intracortically and lead to inhibition of thalamocortical neurons, via activation of thalamic reticular neurons, which may explain the obliteration of signals from the external world and unconsciousness during some paroxysmal states.

Animals↗
PubMed2004

Selective amplification of neocortical neuronal output by fast prepotentials in vivo.

Neocortical cells integrate inputs from thousands of presynaptic neurons distributed along their dendritic arbors. Propagation of postsynaptic potentials to the soma is crucial in determining neuronal output. Using intracellular recordings in anesthetized and non-anesthetized, naturally awake and sleeping cats, we found evidence for generation of fast, all-or-none events recorded at the soma in about 20% of regular-spiking and intrinsically-bursting neurons. These events, termed fast prepotentials (FPPs), were suppressed by hyperpolarizing the neurons or by inhibiting synaptic transmission with perfusion of Ca2+-free artificial cerebrospinal fluid. FPPs could be evoked by activation of specific cortical inputs and allowed neurons to fire at more hyperpolarized levels of membrane potentials. Thus, FPPs represent a powerful mechanism to boost the output of neocortical neurons in response to given inputs. We further found evidence for modulation of FPPs generation across the waking-sleep cycle, indicating important changes in the integrative properties of neocortical neurons in different states of vigilance. We suggest that FPPs represent attenuated spikes generated in hot spots of the dendritic arbor and constitute a powerful mechanism to reinforce the functional connections between specific elements of the cortical networks.

Animals↗
PubMed2004

Potassium model for slow (2-3 Hz) in vivo neocortical paroxysmal oscillations.

In slow neocortical paroxysmal oscillations, the de- and hyperpolarizing envelopes in neocortical neurons are large compared with slow sleep oscillations. Increased local synchrony of membrane potential oscillations during seizure is reflected in larger electroencephalographic oscillations and the appearance of spike- or polyspike-wave complex recruitment at 2- to 3-Hz frequencies. The oscillatory mechanisms underlying this paroxysmal activity were investigated in computational models of cortical networks. The extracellular K(+) concentration ([K(+)](o)) was continuously computed based on neuronal K(+) currents and K(+) pumps as well as glial buffering. An increase of [K(+)](o) triggered a transition from normal awake-like oscillations to 2- to 3-Hz seizure-like activity. In this mode, the cells fired periodic bursts and nearby neurons oscillated highly synchronously; in some cells depolarization led to spike inactivation lasting 50-100 ms. A [K(+)](o) increase, sufficient to produce oscillations could result from excessive firing (e.g., induced by external stimulation) or inability of K(+) regulatory system (e.g., when glial buffering was blocked). A combination of currents including high-threshold Ca(2+), persistent Na(+) and hyperpolarization-activated depolarizing (I(h)) currents was sufficient to maintain 2- to 3-Hz activity. In a network model that included lateral K(+) diffusion between cells, increase of [K(+)](o) in a small region was generally sufficient to maintain paroxysmal oscillations in the whole network. Slow changes of [K(+)](o) modulated the frequency of bursting and, in some case, led to fast oscillations in the 10- to 15-Hz frequency range, similar to the fast runs observed during seizures in vivo. These results suggest that modifications of the intrinsic currents mediated by increase of [K(+)](o) can explain the range of neocortical paroxysmal oscillations in vivo.

Animals↗
PubMed2004

Neocortical seizures: initiation, development and cessation.

Different forms of electrical paroxysms in experimental animals mimic the patterns of absence seizures associated with spike-wave complexes at approximately 3 Hz and of Lennox-Gastaut seizures with spike-wave or polyspike-wave complexes at approximately 1.5-2.5 Hz, intermingled with fast runs at 10-20 Hz. Both these types of electrical seizures are preferentially generated during slow-wave sleep. Here, we challenge the hypothesis of a subcortical pacemaker that would account for suddenly generalized spike-wave seizures as well as the idea of an exclusive role of synaptic excitation in the generation of paroxysmal depolarizing components, and we focus on three points, based on multiple intracellular and field potential recordings in vivo that are corroborated by some clinical studies: (a) the role of neocortical bursting neurons, especially fast-rhythmic-bursting neurons, and of very fast oscillations (ripples, 80-200 Hz) in seizure initiation; (b) the cortical origin of both these types of electrical paroxysms, the synaptic propagation of seizures from one to other, local and distant, cortical sites, finally reaching the thalamus, where the synchronous cortical firing excites thalamic reticular inhibitory neurons and thus leads to steady hyperpolarization and phasic inhibitory postsynaptic potentials in a majority of thalamocortical neurons, which might explain the obliteration of signals from the external world and the unconsciousness during absence seizures; and (c) the cessation of seizures, whose cellular mechanisms have only begun to be investigated and remain an open avenue for research.

Animals↗
PubMed2004

Synaptic responsiveness of neocortical neurons to callosal volleys during paroxysmal depolarizing shifts.

Based on intracellular recordings in vivo, we investigated the responsiveness of cat neocortical neurons to callosal volleys during different phases of spontaneously occurring or electrically induced electrographic seizures, compared with control periods of slow sleep-like oscillations. Overt seizures, with spiking, triggered by pulse-trains to the callosal pathway, started with a latency of approximately 20 s after cessation of stimulation, thus contrasting with paroxysmal activity elicited by ipsilateral cortical or thalamic stimulation that is initiated immediately after electrical stimulation. During the rather long preparatory period to callosally triggered seizures, cortical neurons displayed subthreshold depolarizing runs at 4-7 Hz, associated with increased amplitudes of excitatory postsynaptic potentials. The sequential analysis of neuronal responsiveness during different components of spike-wave complexes revealed progressively increased amplitudes of callosally evoked postsynaptic excitatory responses in regular-spiking and fast-rhythmic-bursting neurons, over a period of approximately 20 ms prior to the generation of paroxysmal depolarizing shifts. These data support the concept that seizures consisting of spike-wave complexes originate within the neocortex through a progressive synaptic buildup and that their synchronization is achieved, at least partially, by cortical commissural synaptic linkages.

Animals↗
PubMed2004

Slow-wave sleep: serotonin, neuronal plasticity, and seizures.

This article starts by enumerating several data that vindicate Michel Jouvet's hypothesis regarding serotonin as a factor promoting slow-wave sleep. The core of the article is devoted to the description of neuronal bases underlying sleep oscillations, with emphasis on the cortically generated slow oscillation (0.5-1 Hz) that groups both low-frequency (spindles and delta) and high-frequency (beta/gamma) rhythms. The low-frequency rhythms are generated by the synchronous firing of cortical neurons during the depolarizing phase of the slow oscillation, which impacts on the thalamic circuitry to generate spindles and clock-like delta potentials. The fast activity is voltage-dependent and occurs during the depolarization component of the slow cortical oscillation. This coalescence of brain rhythms, discovered in intracellular studies of neocortical and thalamic neurons, is now supported by EEG studies during human sleep. The rich spontaneous activity of neocortical neurons during slow-wave sleep is associated with neuronal plasticity that may play a role in consolidating memory traces acquired during the state of waking. Surprisingly, neuronal plasticity, usually regarded as a beneficial phenomenon implicated in memory and learning, could develop during slow-wave sleep into self-sustained paroxysmal discharges, similar to spike-wave complexes that appear in some epileptic syndromes.

Animals↗
PubMed2003

Hyperpolarisation rectification in cat lateral geniculate neurons modulated by intact corticothalamic projections.

The intrinsic properties of thalamic neurons are influenced by synaptic activities in ascending pathways and corticofugal projections, as well as by the actions of neurotransmitters released by generalised modulatory systems. We focused on the effects of corticothalamic projections on the hyperpolarisation-activated cation current Ih. Intracellular recordings of thalamocortical neurons in the dorsal lateral geniculate (dLG) nucleus were performed in cats under ketamine-xylazine anaesthesia. At variance with the conventional way of recording intracellularly from thalamic neurons after partial or total ablation of the grey and white matter overlying the dLG, we preserved intact corticothalamic neuronal loops. Stimulating electrodes inserted into the optic tract and light-emitting-diodes as photic stimulation were used to identify the dLG neurons. The expression of the depolarising sag due to Ih depended on the state of cortical networks. Thalamic dLG Ih, induced by hyperpolarising current steps, was detected during the periods of cortical disfacilitation that occur during the cortical slow (< 1 Hz) oscillation, whereas Ih was absent during the active (depolarised) periods. The possibility that the excitatory corticothalamic projections could preclude the generation of the Ih was tested by applying a concentrated K+ solution (3 M) to the primary visual cortex. The same dLG neurons that did not display Ih before application of K+ were able to produce hyperpolarisation-activated depolarising sags during K+-induced cortical depression. Our data suggest that the thalamic clock-like delta oscillation, which results from an interplay between Ih and the low-threshold calcium current (IT), as described in preparations without cerebral cortex, is prevented in dLG neurons when corticothalamic loops are intact.

Action Potentials↗
PubMed2003

Spontaneous field potentials influence the activity of neocortical neurons during paroxysmal activities in vivo.

Field-potential recordings with macroelectrodes, and extra- and intracellular potentials with micropipettes were used to determine the influence of spontaneous field potentials on the activity of neocortical neurons during seizures. In vivo experiments were carried out in cats under anesthesia. Strong negative field fluctuations of up to 20 mV were associated with electroencephalogram "spikes" during spontaneously occurring paroxysmal activities. During paroxysmal events, action potentials displayed an unexpected behavior: a more hyperpolarized firing threshold and smaller amplitude than during normal activity, as determined with intracellular recordings referenced to a distant ground. Considering the transmembrane potential (the difference between extra- and intracellular potential) qualified this observation: firing threshold determined from the transmembrane potential did not decrease, and smaller action-potential amplitude was associated with depolarized firing threshold. The hyperpolarization of intracellular firing threshold was thus related to the field potentials. Similar field-potential effects on neuronal activities were observed when the paroxysmal events included very fast oscillations or ripples (80-200 Hz) that represent rapid fluctuations of field potentials (up to 5 mV in <5 ms). Neuronal firing was phase-locked to those oscillations. These results demonstrate that: (a) strong spontaneous field potentials influence neuronal behavior, and thus play an active role during paroxysmal activities; and (b) transmembrane potentials have to be used to accurately describe the behavior of neurons in conditions in which field potentials fluctuate strongly. Since neuronal activity is presumably the main generator of field potentials, and in return these potentials may increase neuronal excitability, we propose that this constitutes a positive feedback loop that is involved in the development and spread of paroxysmal activities, and that a similar feedback loop is involved in the generation of neocortical ripples. We propose a mechanism for seizure initiation involving these phenomena.

Animals↗
PubMed2003

Sleep oscillations developing into seizures in corticothalamic systems.

PURPOSE: The aim of this article is to discuss the neuronal substrates of sleep oscillations leading to seizures consisting of spike-wave (SW) complexes at 2-4 Hz, mimicking those seen in absence epilepsy, or SW and polyspike-wave (PSW) complexes at 1.5-2.5 Hz, often associated with fast runs at 10-15 Hz, as in the Lennox-Gastaut syndrome. METHODS: Extracellular recordings were done in permanently implanted animals during the natural waking-sleep cycle. Single and dual simultaneous recordings from cortical neurons, cortical and thalamic neurons, or cortical neurons and glial cells were performed in cats under ketamine-xylazine anesthesia. RESULTS: (a) The minimal substrate of SW seizures is the neocortex because such seizures may occur in thalamectomized animals, in which spindles are absent. In intact-brain animals, SW seizures are initiated in neocortex and spread to the thalamus after a few seconds. The majority of thalamocortical (TC) neurons are steadily hyperpolarized throughout the cortical SW seizures. (b) In the Lennox-Gastaut syndrome, the paroxysmal depolarizing shifts (PDSs) associated with the EEG "spike" of SW/PSW complexes contain an important inhibitory component, whereas the hyperpolarization during the EEG "wave" component is not due to gamma-aminobutryic acid (GABA)ergic inhibitory postsynaptic potentials (IPSPs) but is ascribed to a mixture of disfacilitation and K+ currents. As is also the case with seizures consisting of pure SW complexes, the majority of TC neurons are hyperpolarized during the cortical paroxysms and disinhibited after the cessation of cortical seizures. CONCLUSIONS: Seizures with SW complexes and of the Lennox-Gastaut type preferentially evolve from sleep oscillations. They are initiated in neocortex and spread to the thalamus after a few seconds. The majority of TC neurons are inhibited during these seizures.

Animals↗
PubMed2002

The role of chloride-dependent inhibition and the activity of fast-spiking neurons during cortical spike-wave electrographic seizures.

The conventional view is that the cortical paroxysmal depolarizing shift is a giant excitatory postsynaptic potential enhanced by various intrinsic neuronal currents. Other results point out, however, that synaptic inhibition remains functional in many forms of paroxysmal activities and that intense activation of GABAergic interneurons may accentuate the excitation of target pyramidal cells. To determine the role played by cortical inhibitory neurons in paroxysmal discharges, we used single and dual intracellular recordings from electrophysiologically identified neocortical neurons during spontaneously occurring and electrically induced spike-wave electrographic seizures in vivo. Conventional fast-spiking neurons (presumably local inhibitory interneurons) fired at a very high frequency during paroxysmal depolarizing shifts, which corresponded to the electroencephalogram 'spike' components of spike-wave complexes. The firing of fast-spiking neurons preceded the discharges of neighboring regular-spiking neurons. During electrographic seizures, the reversal potential of the GABA (type A)-mediated potentials in regular-spiking neurons was shifted to positive values by 20-30 mV. Data also show that the prolonged hyperpolarizations during the electroencephalogram 'wave' components of spike-wave electrographic seizures do not contain Cl(-)-dependent inhibitory potentials. Moreover, Cl(-)-dependent mechanisms were reduced or absent during the fast runs that are associated with spike-wave complexes in some paroxysms. We conclude that the strong activity of cortical inhibitory neurons during paroxysmal depolarizing shifts induces Cl(-)-dependent depolarizing postsynaptic potentials in target pyramidal neurons, which facilitate the development of electrographic seizures.

Action Potentials↗
PubMed2001

Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: an intracellular study.

Earlier extracellular recordings during natural sleep have shown that, during slow-wave sleep (SWS), neocortical neurons display long-lasting periods of silence, whereas they are tonically active and discharge at higher rates during waking and sleep with rapid eye movements (REMs). We analyzed the nature of long-lasting periods of neuronal silence in SWS and the changes in firing rates related to ocular movements during REM sleep and waking using intracellular recordings from electrophysiologically identified neocortical neurons in nonanesthetized and nonparalyzed cats. We found that the silent periods during SWS are associated with neuronal hyperpolarizations, which are due to a mixture of K(+) currents and disfacilitation processes. Conventional fast-spiking neurons (presumably local inhibitory interneurons) increased their firing rates during REMs and eye movements in waking. During REMs, the firing rates of regular-spiking neurons from associative areas decreased and intracellular traces revealed numerous, short-lasting, low-amplitude inhibitory postsynaptic potentials (IPSPs), that were reversed after intracellular chloride infusion. In awake cats, regular-spiking neurons could either increase or decrease their firing rates during eye movements. The short-lasting IPSPs associated with eye movements were still present in waking; they preceded the spikes and affected their timing. We propose that there are two different forms of firing rate control: disfacilitation induces long-lasting periods of silence that occur spontaneously during SWS, whereas active inhibition, consisting of low-amplitude, short-lasting IPSPs, is prevalent during REMs and precisely controls the timing of action potentials in waking.

Animals↗
PubMed2001

Natural waking and sleep states: a view from inside neocortical neurons.

In this first intracellular study of neocortical activities during waking and sleep states, we hypothesized that synaptic activities during natural states of vigilance have a decisive impact on the observed electrophysiological properties of neurons that were previously studied under anesthesia or in brain slices. We investigated the incidence of different firing patterns in neocortical neurons of awake cats, the relation between membrane potential fluctuations and firing rates, and the input resistance during all states of vigilance. In awake animals, the neurons displaying fast-spiking firing patterns were more numerous, whereas the incidence of neurons with intrinsically bursting patterns was much lower than in our previous experiments conducted on the intact-cortex or isolated cortical slabs of anesthetized cats. Although cortical neurons displayed prolonged hyperpolarizing phases during slow-wave sleep, the firing rates during the depolarizing phases of the slow sleep oscillation was as high during these epochs as during waking and rapid-eye-movement sleep. Maximum firing rates, exceeding those of regular-spiking neurons, were reached by conventional fast-spiking neurons during both waking and sleep states, and by fast-rhythmic-bursting neurons during waking. The input resistance was more stable and it increased during quiet wakefulness, compared with sleep states. As waking is associated with high synaptic activity, we explain this result by a higher release of activating neuromodulators, which produce an increase in the input resistance of cortical neurons. In view of the high firing rates in the functionally disconnected state of slow-wave sleep, we suggest that neocortical neurons are engaged in processing internally generated signals.

Action Potentials↗
PubMed2001

Impact of network activities on neuronal properties in corticothalamic systems.

Data from in vivo and in vitro experiments are discussed to emphasize that synaptic activities in neocortex and thalamus have a decisive impact on intrinsic neuronal properties in intact-brain preparations under anesthesia and even more so during natural states of vigilance. Thus the firing patterns of cortical neuronal types are not inflexible but may change with the level of membrane potential and during periods rich in synaptic activity. The incidences of some cortical cell classes (defined by their responses to depolarizing current pulses) are different in isolated cortical slabs in vivo or in slices maintained in vitro compared with the intact cortex of naturally awake animals. Network activities, which include the actions of generalized modulatory systems, have a profound influence on the membrane potential, apparent input resistance, and backpropagation of action potentials. The analysis of various oscillatory types leads to the conclusion that in the intact brain, there are no "pure" rhythms, generated in simple circuits, but complex wave sequences (consisting of different, low- and fast-frequency oscillations) that result from synaptic interactions in corticocortical and corticothalamic neuronal loops under the control of activating systems arising in the brain stem core or forebrain structures. As an illustration, it is shown that the neocortex governs the synchronization of network or intrinsically generated oscillations in the thalamus. The rhythmic recurrence of spike bursts and spike trains fired by thalamic and cortical neurons during states of decreased vigilance may lead to plasticity processes in neocortical neurons. If these phenomena, which may contribute to the consolidation of memory traces, are not constrained by inhibitory processes, they induce seizures in which the neocortex initiates the paroxysms and controls their thalamic reflection. The results indicate that intact-brain preparations are necessary to investigate global brain functions such as behavioral states of vigilance and paroxysmal activities.

Action Potentials↗
PubMed2001

Focal synchronization of ripples (80-200 Hz) in neocortex and their neuronal correlates.

Field potentials from different neocortical areas and intracellular recordings from areas 5 and 7 in acutely prepared cats under ketamine-xylazine anesthesia and during natural states of vigilance in chronic experiments, revealed the presence of fast oscillations (80-200 Hz), termed ripples. During anesthesia and slow-wave sleep, these oscillations were selectively related to the depth-negative (depolarizing) component of the field slow oscillation (0.5-1 Hz) and could be synchronized over ~10 mm. The dependence of ripples on neuronal depolarization was also shown by their increased amplitude in field potentials in parallel with progressively more depolarized values of the membrane potential of neurons. The origin of ripples was intracortical as they were also detected in small isolated slabs from the suprasylvian gyrus. Of all types of electrophysiologically identified neocortical neurons, fast-rhythmic-bursting and fast-spiking cells displayed the highest firing rates during ripples. Although linked with neuronal excitation, ripples also comprised an important inhibitory component. Indeed, when regular-spiking neurons were recorded with chloride-filled pipettes, their firing rates increased and their phase relation with ripples was modified. Thus besides excitatory connections, inhibitory processes probably play a major role in the generation of ripples. During natural states of vigilance, ripples were generally more prominent during the depolarizing component of the slow oscillation in slow-wave sleep than during the states of waking and rapid-eye movement (REM) sleep. The mechanisms of generation and synchronization, and the possible functions of neocortical ripples in plasticity processes are discussed.

Action Potentials↗