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M Steriade

Publications and source records attributed to M Steriade.

At least 55 records · Page 3Linked to original sources
PubMed1998

Cellular substrates and laminar profile of sleep K-complex.

We describe the cellular mechanisms that underlie the generation of the K-complex, a major grapho-element of sleep electroencephalogram in humans. First we demonstrate the similarity between K-complexes recorded during natural sleep and under ketamine-xylazine anaesthesia in cats. Thereafter, we show by means of multi-site cellular and field potential recordings that K-complexes are rhythmic at frequencies of less than 1 Hz (mainly 0.5-0.9 Hz) and that they are synchronously distributed over the whole cortical surface as well as transferred to the thalamus. The surface K-complex reverses its polarity at a cortical depth of about 0.3 mm. At the cortical depth, the K-complex is made of a sharp and high-amplitude negative deflection that reflects cellular depolarization, often preceded by a smaller-amplitude, positive slow-wave reflecting cellular hyperpolarization. The sharp component of the K-complex may lead to a spindle sequence and/or to fast (mainly 20-50 Hz) oscillations. K-complexes appear spontaneously or triggered by cortical or thalamic stimulation, and they arise within cortical networks. We suggest that K-complexes, either in isolation or followed by a brief sequence of spindle waves, are the expression of the spontaneously occurring, cortically generated slow oscillation.

Algorithms↗
PubMed1998

Slow sleep oscillation, rhythmic K-complexes, and their paroxysmal developments.

This paper presents the relations between the slow (< 1 Hz) oscillation (characterizing the activity of corticothalamic networks during quiescent sleep in cats and humans), sleep K-complexes, and some paroxysmal developments of sleep patterns. At the cellular level, the slow oscillation is built up by rhythmic membrane depolarizations and hyperpolarizations of cortical neurons. The EEG expression of this activity is marked by periodic K-complexes which reflect neuronal excitation. The slow oscillation triggers, groups and synchronizes other sleep rhythms, such as thalamically generated spindles as well as thalamically and cortically generated delta oscillations. We discuss the distinctness of the slow (< 1 Hz) and delta (1-4 Hz) oscillations. We also show that the slow cortical oscillation underlies the onset of spike-wave seizures during sleep by transforming the periodic K-complexes into recurrent paroxysmal spike-wave complexes.

Animals↗
PubMed1998

Dynamic properties of corticothalamic neurons and local cortical interneurons generating fast rhythmic (30-40 Hz) spike bursts.

Fast spontaneous oscillations (mainly 30-40 Hz) characterize cortical and thalamic neuronal networks during behavioral states of increased vigilance and depend on cell depolarization under the influence of ascending activating systems. We investigated, by means of intracellular recording and staining in vivo, the properties of fast-oscillating cortical neurons from cat's motor and association areas, some projecting to the thalamus, others with locally arborizing axons. At a given level of depolarization, 28% of our neuronal sample discharged high-frequency spike bursts (300-600 Hz) that recurred rhythmically between 20 and 50 Hz. Such fast rhythmic bursting neurons have been found in both superficial and deep cortical layers. Slight changes in membrane potential as well as synaptic activity in thalamocortical networks dramatically altered the discharge patterns, from single spikes to rhythmic spike-bursts, and eventually to fast tonic firing without frequency adaptation. Thus our data challenge the conventional idea that sharply defined, invariant features and distinct locations in certain cortical layers characterize some neocortical cell-classes. We demonstrate that the distinctions between intrinsic electrophysiological properties of neocortical neurons are much more labile than conventionally thought. The present results, which indicate that corticothalamic neurons discharge fast rhythmic spike bursts mainly at 30-40 Hz, suggest that this activity results in integrated fast oscillations within corticothalamic networks.

Animals↗
PubMed1998

Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells.

Early studies have shown that spindle oscillations are generated in the thalamus and are synchronized over wide cortical territories. More recent experiments have shown that this large-scale synchrony depends on the integrity of corticothalamic feedback. Previously proposed mechanisms emphasized exclusively intrathalamic mechanisms to generate the synchrony of these oscillations. In the present paper, we propose a cellular mechanism in which the synchrony is dependent of a mutual interaction between cortex and thalamus. This cellular mechanism is tested by computational models consisting of pyramidal cells, interneurons, thalamic reticular (RE) and thalamocortical (TC) relay cells, on the basis of voltage-clamp data on intrinsic currents and synaptic receptors present in the circuitry. The model suggests that corticothalamic feedback must operate on the thalamus mainly through excitation of GABAergic RE neurons, therefore recruiting relay cells essentially through inhibition and rebound. We provide experimental evidence for such dominant inhibition in the lateral posterior nucleus. In these conditions, the model shows that cortical discharges optimally evoked thalamic oscillations. This feature is essential to the present cellular mechanism and is also consistently observed experimentally. The model further shows that, with this type of corticothalamic feedback, cortical discharges recruited large areas of the thalamus because of the divergent cortex-to-RE and RE-to-TC axonal projections. Consequently, the thalamocortical network generated patterns of oscillations and synchrony similar to in vivo recordings. The model also emphasizes the important role of the modulation of the Ih current by calcium in TC cells. This property conferred a relative refractoriness to the entire network, a feature also observed experimentally, as we show here. Further, the same property accounted for various spatiotemporal features of oscillations, such as systematic propagation after low-intensity cortical stimulation, local oscillations, and more generally, a high variability in the patterns of spontaneous oscillations, similar to in vivo recordings. We propose that the large-scale synchrony of spindle oscillations in vivo is the result of thalamocortical interactions in which the corticothalamic feedback acts predominantly through the RE nucleus. Several predictions are suggested to test the validity of this model.

Animals↗
PubMed1998

Cellular mechanisms underlying intrathalamic augmenting responses of reticular and relay neurons.

Augmenting (or incremental) responses are progressively growing potentials elicited by 5- to 15-Hz stimulation within the thalamus, cerebral cortex, or by setting into action reciprocal thalamocortical neuronal loops. These responses are associated with short-term plasticity processes in thalamic and cortical neurons. In the present study, in vivo intracellular recordings of thalamic reticular (RE) and thalamocortical (TC), as well as dual intracellular recordings, were used to explore the mechanisms of two types of intrathalamic augmenting responses elicited by thalamic stimuli at 10 Hz in decorticated cats. As recently described, after decortication, TC cells display incremental burst responses to thalamic stimuli that occur through either progressive depolarization (high threshold, HT) or progressive hyperpolarization leading to deinactivation of low-threshold (LT) spike bursts. Here, low-intensity stimuli (10 Hz) to dorsal thalamic nuclei elicited decremental responses in GABAergic RE cells, consisting of a progressive diminution in the number of action potentials in successive spike bursts, whereas higher stimulation (>50% of maximal strength) induced augmentation characterized by an increased number of spikes in repetitive responses. These opposing discharge patterns occurred in the absence of changes in the membrane potential of RE cells. In TC cells, augmentation depended on the thalamic site where testing volleys were applied. With stimuli applied closer to the site of impalement, augmenting resulted from a transformation from LT spike bursts into HT responses. Augmenting responses were followed by self-sustained oscillatory activity, within the frequency of spindles (7-14 Hz) or clock-like delta oscillation (1-4 Hz). As LT augmentation in TC cells results from their progressive hyperpolarization, we tested the effects exerted by the activating depolarizing system arising in the mesopontine cholinergic nuclei and found that such conditioning pulse-trains prevented the hyperpolarizing-rebound sequences as well as the LT augmenting in TC cells. We propose that the depolarization-dependent (HT) augmenting responses in TC cells result from decremental responses in RE neurons that are due to intra-RE inhibitory processes leading to disinhibition in target TC neurons, whereas LT-type augmenting in TC cells is produced mainly by incremental responses in GABAergic RE neurons.

Action Potentials↗
PubMed1998

Cellular and network models for intrathalamic augmenting responses during 10-Hz stimulation.

Repetitive stimulation of the thalamus at 7-14 Hz evokes responses of increasing amplitude in the thalamus and the areas of the neocortex to which the stimulated foci project. Possible mechanisms underlying the thalamic augmenting responses during repetitive stimulation were investigated with computer models of interacting thalamocortical (TC) and thalamic reticular (RE) cells. The ionic currents in these cells were modeled with Hodgkin-Huxley type of kinetics, and the results of the model were compared with in vivo thalamic recordings from decorticated cats. The simplest network model demonstrating an augmenting response was a single pair of coupled RE and TC cells, in which RE-induced inhibitory postsynaptic potentials (IPSPs) in the TC cell led to progressive deinactivation of a low-threshold Ca2+ current. The augmenting responses in two reciprocally interacting chains of RE and TC cells depended also on gamma-aminobutyric acid-B (GABAB) IPSPs. Lateral GABAA inhibition between identical RE cells, which weakened bursts in these cells, diminished GABAB IPSPs and delayed the augmenting response in TC cells. The results of these simulations show that the interplay between existing mechanisms in the thalamus explains the basic properties of the intrathalamic augmenting responses.

Animals↗
PubMed1998

Spike-wave complexes and fast components of cortically generated seizures. I. Role of neocortex and thalamus.

We explored the relative contributions of cortical and thalamic neuronal networks in the generation of electrical seizures that include spike-wave (SW) and polyspike-wave (PSW) complexes. Seizures were induced by systemic or local cortical injections of bicuculline, a gamma-aminobutyric acid-A (GABAA) antagonist, in cats under barbiturate anesthesia. Field potentials and extracellular neuronal discharges were recorded through arrays of eight tungsten electrodes (0.4 or 1 mm apart) placed over the cortical suprasylvian gyrus and within the thalamus. 1) Systemic injections of bicuculline induced SW/PSW seizures in cortex, whereas spindle sequences continued to be present in the thalamus. 2) Cortical suprasylvian injection of bicuculline induced focal paroxysmal single spikes that developed into full-blown seizures throughout the suprasylvian cortex. The seizures were characterized by highly synchronized SW or PSW complexes at 2-4 Hz, interspersed with runs of fast (10-15 Hz) activity. The intracellular aspects of this complex pattern in different types of neocortical neurons are described in the following paper. Complete decortication abolished the seizure, leaving intact thalamic spindles. Injections of bicuculline in the cortex of athalamic cats resulted in similar components as those occurring with an intact thalamus. 3) Injection of bicuculline in the thalamus decreased the frequency of barbiturate spindles and increased the synchrony of spike bursts fired by thalamocortical and thalamic reticular cells but did not induce seizures. Decortication did not modify the effects of bicuculline injection in the thalamus. Our results indicate that the minimal substrate that is necessary for the production of seizures consisting of SW/PSW complexes and runs of fast activity is the neocortex.

Animals↗
PubMed1998

Spike-wave complexes and fast components of cortically generated seizures. II. Extra- and intracellular patterns.

In the previous paper we have demonstrated, by means of field potential and extracellular unit recordings, that bicuculline-induced seizures, which include spike-wave (SW) or polyspike-wave (PSW) complexes, are initiated intracortically and survive ipsilateral thalamectomy. Here, we used multisite field potential and extracellular recordings to validate the patterns of cortical SW/PSW seizures in chronically implanted, behaving cats. To investigate the cellular patterns and excitability during spontaneously occurring and electrically elicited cortical seizures, we used single and dual intracellular recordings from regular-spiking (RS) and fast-rhythmic-bursting (FRB) cortical neurons, in conjunction with field potential recordings from neocortex and related thalamic nuclei, in cats maintained under ketamine-xylazine anesthesia. 1) Invariably, the spontaneous or electrically induced seizures were initiated within the cortex of both behaving and anesthetized animals. Spontaneously occurring, compound seizures consisting of SW/PSW complexes at 2-4 Hz and fast runs at 10-15 Hz, developed without discontinuity from the slow (mainly 0.5-0.9 Hz), sleeplike, cortically generated oscillation. 2) During SW/PSW complexes, RS neurons discharged spike trains during the depth-negative component of the cortical "spike" component of field potentials and were hyperpolarized during the depth-positive field wave. The FRB neurons fired many more action potentials than RS cells during SW/PSW complexes. Averaged activities triggered by the spiky field potentials or by the steepest slope of depolarization in cortical neurons demonstrated similar relations between intracellular activities and field potentials during sleep and seizure epochs, the latter-being an exaggeration of the depolarizing and hyperpolarizing components of the slow sleep oscillation. 3) During the fast runs, RS cells were tonically depolarized and discharged single action potentials or spike doublets (usually with pronounced spike inactivation), whereas FRB cells discharged rhythmic spike bursts, time locked with the depth-negative field potentials. 4) Neuronal excitability, tested by depolarizing current pulses applied throughout the seizures and compared with pre- and postseizure epochs, showed a decreased number of evoked action potentials during both seizure components (SW/PSW complexes and fast runs), eventually leading to null responses during the postictal depression. 5) Data suggest that interconnected FRB neurons may play an important role in the initiation of cortical seizures. We discuss the similarities between the electrographic patterns described in this study and those found in different forms of clinical seizures.

Anesthesia↗
PubMed1998

Spike-wave complexes and fast components of cortically generated seizures. III. Synchronizing mechanisms.

The intracortical and thalamocortical synchronization of spontaneously occurring or bicuculline-induced seizures, consisting of spike-wave (SW) or polyspike-wave (PSW) complexes at 2-3 Hz and fast runs at 10-15 Hz, was investigated in cats under ketamine-xylazine anesthesia. We used single and dual simultaneous intracellular recordings from cortical areas 5 and 7, and extracellular recordings of unit firing and field potentials from neocortical areas 5, 7, 17, 18, as well as related thalamic nuclei. The evolution of time delays between paroxysmal depolarizing events in single neurons or neuronal pools recorded from adjacent and distant sites was analyzed by using 1) sequential cross-correlations between field potentials, 2) averaged activities triggered by the spiky component of cortical SW/PSW complexes, and 3) time histograms between neuronal discharges. In all instances, the paroxysmal activities recorded from the dorsal thalamus lagged the onset of seizures in neocortex. The time lags between simultaneously impaled cortical neurons were significantly smaller during SW complexes than during the prior epochs of slow oscillation. During seizures, as during the slow oscillation, the intracortical synchrony was reduced with increased distance between different cortical sites. Dual intracellular recordings showed that, during the same seizure, time lags were not constant and, instead, reflected alternating precession of the recorded foci. After transection between areas 5 and 7, the intracortical synchrony was lost, but corticothalamocortical volleys could partially restore seizure synchrony. These data show that the neocortex leads the thalamus during SW/PSW seizures, that time lags between cortical foci are not static, and that thalamus may assist synchronization of SW/PSW seizures after disconnection of intracortical synaptic linkages.

Anesthesia↗
PubMed1998

Spike-wave complexes and fast components of cortically generated seizures. IV. Paroxysmal fast runs in cortical and thalamic neurons.

In the preceding papers of this series, we have analyzed the cellular patterns and synchronization of neocortical seizures occurring spontaneously or induced by electrical stimulation or cortical infusion of bicuculline under a variety of experimental conditions, including natural states of vigilance in behaving animals and acute preparations under different anesthetics. The seizures consisted of two distinct components: spike-wave (SW) or polyspike-wave (PSW) at 2-3 Hz and fast runs at 10-15 Hz. Because the thalamus is an input source and target of cortical neurons, we investigated here the seizure behavior of thalamic reticular (RE) and thalamocortical (TC) neurons, two major cellular classes that have often been implicated in the generation of paroxysmal episodes. We performed single and dual simultaneous intracellular recordings, in conjunction with multisite field potential and extracellular unit recordings, from neocortical areas and RE and/or dorsal thalamic nuclei under ketamine-xylazine and barbiturate anesthesia. Both components of seizures were analyzed, but emphasis was placed on the fast runs because of their recent investigation at the cellular level. 1) The fast runs occurred at slightly different frequencies and, therefore, were asynchronous in various cortical neuronal pools. Consequently, dorsal thalamic nuclei, although receiving convergent inputs from different neocortical areas involved in seizure, did not express strongly synchronized fast runs. 2) Both RE and TC cells were hyperpolarized during seizure episodes with SW/PSW complexes and relatively depolarized during the fast runs. As known, hyperpolarization of thalamic neurons deinactivates a low-threshold conductance that generates high-frequency spike bursts. Accordingly, RE neurons discharged prolonged high-frequency spike bursts in close time relation with the spiky component of cortical SW/PSW complexes, whereas they fired single action potentials, spike doublets, or triplets during the fast runs. In TC cells, the cortical fast runs were reflected as excitatory postsynaptic potentials appearing after short latencies that were compatible with monosynaptic activation through corticothalamic pathways. 3) The above data suggested the cortical origin of these seizures. To further test this hypothesis, we performed experiments on completely isolated cortical slabs from suprasylvian areas 5 or 7 and demonstrated that electrical stimulation within the slab induces seizures with fast runs and SW/PSW complexes, virtually identical to those elicited in intact-brain animals. The conclusion of all papers in this series is that complex seizure patterns, resembling those described at the electroencephalogram level in different forms of clinical seizures with SW/PSW complexes and, particularly, in the Lennox-Gastaut syndrome of humans, are generated in neocortex. Thalamic neurons reflect cortical events as a function of membrane potential in RE/TC cells and degree of synchronization in cortical neuronal networks.

Adrenergic alpha-Agonists↗
PubMed1998

Coalescence of sleep rhythms and their chronology in corticothalamic networks.

The cellular substrates of sleep oscillations have recently been investigated by means of multi-site, intracellular and extracellular recordings under anesthesia, and these data have been validated during natural sleep in cats and humans. Although various rhythms occurring during the state of resting sleep (spindle, 7-14 Hz; delta, 1-4 Hz; and slow oscillation, <1 Hz) are conventionally described by using their different frequencies, they are coalesced within complex wave-sequences due to the synchronizing power of the cortically generated slow oscillation (main peak around 0.7 Hz). In intracellular recordings from anesthetized animals, the slow oscillation is characterized by a biphasic sequence consisting of a prolonged hyperpolarization and depolarization. Basically similar patterns are observed by means of extracellular discharges and/or field potentials in naturally sleeping animals and humans. The depolarizing component of the slow oscillation is transferred to the thalamus where it contributes to the synchronization of spindles over widespread territories. The association between the depolarizing component of the slow oscillation and the subsequent sequence of spindle waves forms what is termed the K-complex. The slow oscillation also groups cortically generated delta waves. At variance with previous assumptions that the brain lies for the most part in the dark and a global inhibition occurs in resting sleep, cortical cells are quite active in this behavioral state. This unexpectedly rich activity raises the possibility that, during sleep, the brain is occupied to specify/reorganize circuits and to consolidate memory traces acquired during wakefulness.

Anesthesia↗
PubMed1997

Fast (mainly 30-100 Hz) oscillations in the cat cerebellothalamic pathway and their synchronization with cortical potentials.

1. Intracellular recordings from 216 thalamocortical (TC) neurones in the ventrolateral (VL) nucleus of intact-cortex and decorticated cats under ketamine-xylazine anaesthesia revealed spontaneously occurring fast oscillations (mainly 30-100 Hz) in 86% of investigated cells. The fast depolarizing events consisted of excitatory postsynaptic potentials (EPSPs), giving rise to fast prepotentials (FPPs) in 22% of neurones, which eventually lead to full-blown action potentials. The frequency of fast events changed by factors of 2-5 in periods as short as 0.3-1.0 s. 2. The spontaneous oscillations were similar to responses evoked in VL relay neurones by stimuli to the afferent cerebellofugal axons in brachium conjunctivum (BC) and were strikingly reduced or abolished after electrolytic lesion of BC axons. 3. The amplitude and duration of fast depolarizing events were significantly reduced during the descending phase of the inhibitory postsynaptic potentials (IPSPs) in TC cells, related to spontaneous spindles or evoked by local thalamic stimulation. 4. Averaged field potentials recorded from motor cortex and triggered by EPSPs and/or action potentials of intracellularly recorded VL cells demonstrated that both spontaneous and BC-evoked fast depolarizations in VL relay neurones were coherent with fast rhythms in cortical area 4. 5. These results show that, in addition to the thalamic and cortical generation sites of the fast (so-called gamma) oscillations, prethalamic relay stations, such as deep cerebellar nuclei, are major contributors to the induction of fast rhythms which depend on the depolarization of thalamic and cortical neurones and which represent a hallmark of brain activation patterns.

Action Potentials↗
PubMed1997

Short-term plasticity during intrathalamic augmenting responses in decorticated cats.

The intrathalamic mechanisms of frequency-dependent augmenting responses were investigated in decorticated cats by means of intracellular recordings from thalamocortical (TC) neurons in ventrolateral (VL) nucleus, including simultaneous impalements from two TC neurons. Pulse trains (10 Hz) applied to VL nucleus elicited two types of augmenting responses: (1) in 68% of cells, the incremental responses occurred on a progressive depolarization associated with the decrease in IPSPs produced by preceding stimuli in the train; (2) in the remaining cells, progressively growing low-threshold (LT) responses resulted from the enhancement of Cl--dependent IPSPs, giving rise to postinhibitory rebound bursts, followed by a self-sustained sequence of spindle waves. Although in some TC cells the augmenting responses developed from LT responses once the latter reached a given level of depolarization, other neurons displayed augmenting responses immediately after the early antidromic spike that depolarized the neuron to the required level, without an intermediate step of LT rebound. Repeated pulse trains led to a progressive and persistent increase in slow depolarizing responses of TC cells, as well as to a persistent and prolonged decrease in the amplitudes of the IPSPs. On the basis of parallel experiments, we propose that the two types of augmentation in TC cells are a result of contrasting responses of thalamic reticular neurons evoked by repetitive thalamic stimuli: decremental responses, which may account for disinhibition leading to depolarizing responses in TC cells, and incremental responses, explaining the progressive hyperpolarization of TC cells. These data demonstrate that frequency-dependent changes in neuronal excitability are present in the thalamus of a decorticated hemisphere and suggest that short-term plasticity processes in the gateway to the cerebral cortex may decisively influence cortical excitability during repetitive responses.

Action Potentials↗
PubMed1997

Instrumental conditioning of fast (20- to 50-Hz) oscillations in corticothalamic networks.

Cats were instrumentally conditioned to generate grouped fast (20- to 50-Hz) oscillations in motor cortex (area 4). Over seven experimental sessions, there was a spatially selective increased generation of grouped fast oscillations in that electroencephalogram lead. This locally increased generation of fast oscillations in cortex was associated with a widespread increase in synchrony of fast oscillations in thalamocortical networks, as demonstrated by cross-correlations between intracortical, corticothalamic, and intrathalamic field potentials. A three-session extinction period abolished the local increase in generation of grouped fast oscillations and reset the thalamocortical synchrony of fast oscillations to control values. A subsequent series of seven sessions with instrumental conditioning of fast oscillations in visual cortex (area 17) reproduced the results from area 4, with a spatially selective increased generation of grouped fast oscillations in the criterion lead, associated with a widespread increase in thalamocortical synchrony of fast oscillations. In addition to their presence during the conditioning sessions, the changes in synchrony of fast oscillations were expressed during periods of quiet waking, rapid-eye-movement sleep, and nonrapid-eye-movement sleep recorded during the first hour after the end of the conditioning.

Animals↗
PubMed1997

Spatiotemporal patterns of spindle oscillations in cortex and thalamus.

Spindle oscillations (7-14 Hz) appear in the thalamus and cortex during early stages of sleep. They are generated by the combination of intrinsic properties and connectivity patterns of thalamic neurons and distributed to cortical territories by thalamocortical axons. The corticothalamic feedback is a major factor in producing coherent spatiotemporal maps of spindle oscillations in widespread thalamic territories. Here we have investigated the spatiotemporal patterns of spontaneously occurring and evoked spindles by means of multisite field potential and unit recordings in intact cortex and decorticated animals. We show that (1) spontaneous spindle oscillations are synchronized over large cortical areas during natural sleep and barbiturate anesthesia; (2) under barbiturate anesthesia, the cortical coherence is not disrupted by transection of intracortical synaptic linkages; (3) in intact cortex animals, spontaneously occurring barbiturate spindle sequences occur nearly simultaneously over widespread thalamic territories; (4) in the absence of cortex, the spontaneous spindle oscillations throughout the thalamus are less organized, but the local coherence (within 2-4 mm) is still maintained; and (5) spindling propagation is observed in intact cortex animals only when elicited by low intensity cortical stimulation, applied shortly before the initiation of a spontaneous spindle sequence; propagation velocities are between 1 and 3 mm/sec, measured in the anteroposterior axis of the thalamus; increasing the intensity of cortical stimulation triggers spindle oscillations, which start simultaneously in all leads. We propose that, in vivo, the coherence of spontaneous spindle oscillations in corticothalamic networks is attributable to the combined action of continuous background corticothalamic input initiating spindle sequences in several thalamic sites at the same time and divergent corticothalamic and intrathalamic connectivity.

Anesthesia↗
PubMed1997

Diffuse transmission by acetylcholine in the CNS.

Recent immunoelectron microscopic studies have revealed a low frequency of synaptic membrane differentiations on ACh (ChAT-immunostained) axon terminals (boutons or varicosities) in adult rat cerebral cortex, hippocampus and neostriatum, suggesting that, besides synaptic transmission, diffuse transmission by ACh prevails in many regions of the CNS. Cytological analysis of the immediate micro-environment of these ACh terminals, as well as currently available immunocytochemical data on the cellular and subcellular distribution of ACh receptors, is congruent with this view. At least in brain regions densely innervated by ACh neurons, a further aspect of the diffuse transmission paradigm is envisaged: the existence of an ambient level of ACh in the extracellular space, to which all tissue elements would be permanently exposed. Recent experimental data on the various molecular forms of AChE and their presumptive role at the neuromuscular junction support this hypothesis. As in the peripheral nervous system, degradation of ACh by the prevalent G4 form of AChE in the CNS would primarily serve to keep the extrasynaptic, ambient level of ACh within physiological limits, rather than totally eliminate ACh from synaptic clefts. Long-lasting and widespread electrophysiological effects imputable to ACh in the CNS might be explained in this manner. The notions of diffuse transmission and of an ambient level of ACh in the CNS could also be of clinical relevance, in accounting for the production and nature of certain cholinergic deficits and the efficacy of substitution therapies.

Acetylcholine↗
PubMed1997

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.

Anesthetics, General↗