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Biomedical subjects

M Steriade

Publications and source records attributed to M Steriade.

At least 145 records · Page 8Linked to original sources

The blockage of ponto-geniculo-occipital waves in the cat lateral geniculate nucleus by nicotinic antagonists.

The cholinergic mechanism underlying the genesis of ponto-geniculo-occipital (PGO) waves recorded from the lateral geniculate (LG) nucleus was studied in reserpinized cats under urethane anesthesia. PGO field potentials and their related unit activities occurred spontaneously or were triggered by stimulation of the brainstem peribrachial (PB) area. It was found that PGO-related unit activities were strongly depressed by systemic or iontophoretic applications of nicotinic antagonists such as mecamylamine or hexamethonium but remained intact after similar applications of scopolamine. These results suggest that the genesis of thalamic PGO waves involves a nicotinic activation of relay neurons by PB cholinergic afferents.

Action Potentials↗

Basal forebrain cholinergic and noncholinergic projections to the thalamus and brainstem in cats and monkeys.

The projections of basal forebrain neurons to the thalamus and the brainstem were investigated in cats and primates by using retrograde transport techniques and choline acetyltransferase (ChAT) immunohistochemistry. In a first series of experiments, the lectin wheat germ-agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into all major sensory, motor, intralaminar, and reticular (RE) thalamic nuclei of cats and into the mediodorsal (MD) and pulvinar-lateroposterior thalamic nuclei of macaque monkeys. In cats numerous neurons of the vertical and horizontal limbs of the diagonal band nucleus and the substantia innominata (SI), including its rostromedial portion termed the ventral pallidum (VP), were retrogradely labeled after WGA-HRP injections in the rostral pole of the RE complex, the MD, and anteroventral/anteromedial (AV/AM) thalamic nuclei. Fewer retrogradely labeled cells were observed in the same areas after injections in the ventromedial (VM) thalamic nucleus, and none or very few after other thalamic injections. After RE, MD, and AV/AM injections, 7-20% of all retrogradely labeled cells in the basal forebrain were also ChAT positive, while none of the retrogradely labeled neurons following VM injections displayed ChAT immunoreactivity. The basal forebrain projection to the MD nucleus was shown to arise principally from VP in both cats and macaque monkeys. In a second series of experiments performed in cats, injections of WGA-HRP in the brainstem peribrachial (PB) area comprising the pedunculopontine nucleus led to retrograde labeling of a moderate number of neurons in the lateral part of the VP, SI, and preoptic area (POA), only a few of which displayed ChAT immunoreactivity. In addition, a large number of retrogradely labeled cells were observed in the bed nuclei of the anterior commissure and stria terminalis after PB injections. In a third series of experiments, the use of the retrograde double-labeling method with fluorescent tracers in squirrel monkeys allowed us to identify a significant number of basal forebrain neurons sending axon collaterals to both the RE thalamic nucleus and PB brainstem area, while no double-labeled neurons were disclosed after injections confined to the ventral anterior/ventral lateral (VA/VL) thalamic nuclei and PB area or following injections in the cerebral cortex and PB area. Our findings reveal the existence of cholinergic and noncholinergic basal forebrain projections to the thalamus and the brainstem in both cats and macaque monkeys. We suggest that these projections may play a crucial role in the control of thalamic functions in mammals.

Animals↗

Cholinergic and non-cholinergic projections from the upper brainstem core to the visual thalamus in the cat.

The projections of cholinergic and non-cholinergic neurons of the rostral brainstem reticular formation to the visual thalamic nuclei (dorsal lateral geniculate - LG, lateral posterior - LP, and perigeniculate - PG) were studied in cat by using the retrograde transport of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) combined with choline acetyltransferase (ChAT) immunohistochemistry. After thalamic injections, less than 10% of all retrogradely labeled neurons in the upper brainstem reticular core were located at most rostral (perirubral) levels where there are virtually no cholinergic elements. Approximately 75-80% of all HRP-positive neurons in the reticular formation were found between stereotaxic planes anterior 1 and posterior 2, in the peribrachial (PB) area of the pedunculopontine nucleus and in the laterodorsal tegmental (LDT) nucleus. The brainstem afferents to LG and PG thalamic nuclei essentially derive from PB neurons, with a small contribution from LDT cells, whereas the LP thalamic nucleus receives massive inputs from both PB and LDT brainstem nuclei. Of all HRP-positive elements visualized in the PB nucleus after an LG or a PG injection, 87% and 73%, respectively, were also ChAT-positive. Of all HRP-positive elements in the PB and LDT nuclei after an LP injection, 82% and 92%, respectively, were also ChAT-positive. The numbers of labeled neurons in the contralateral brainstem reticular nuclei reach 30% to 50% of the numbers found in the ipsilateral reticular formation. These findings reveal the existence of a prominent cholinergic projection from the brainstem reticular formation to the visual thalamic nuclei. Such a chemospecific projection is probably involved in phasic and tonic events of activated behavioral states.

Animals↗

Projections of cholinergic and non-cholinergic neurons of the brainstem core to relay and associational thalamic nuclei in the cat and macaque monkey.

The projections of brainstem core neurons to relay and associational thalamic nuclei were studied in the cat and macaque monkey by combining the retrograde transport of wheat germ agglutinin conjugated with horseradish peroxidase with choline acetyltransferase immunohistochemistry. All major sensory (medial geniculate, lateral geniculate, ventrobasal), motor (ventroanterior, ventrolateral, ventromedial), associational (mediodorsal, pulvinar, lateral posterior) and limbic (anteromedial, anteroventral) thalamic nuclei of the cat were found to receive projections from cholinergic neurons located in the peribrachial area of the pedunculopontine nucleus and in the laterodorsal tegmental nucleus as well as from non-cholinergic neurons in the rostral (perirubral) part of the central tegmental mesencephalic field. Specific relay nuclei receive less than 10% of their brainstem afferents from non-cholinergic neurons located at rostral midbrain levels and receive 85-96% of their brainstem innervation from a region at midbrain-pontine junction where the cholinergic peribrachial area and laterodorsal tegmental nucleus are maximally developed. Of the total number of horseradish peroxidase-positive brainstem neurons seen after injections in various specific relay nuclei, the double-labeled (horseradish peroxidase + choline acetyltransferase) neurons represent approximately 70-85%. Three to eight times more numerous horseradish peroxidase-labeled brainstem cells were found after injections in associational (mediodorsal and pulvinar-lateral posterior complex) and diffusely cortically-projecting (ventromedial) thalamic nuclei of cat than after injections in specific relay nuclei. The striking retrograde cell labeling observed after injections in nuclei with associative functions and widespread cortical projections was due to massive afferentation from non-cholinergic parts of the midbrain and pontine reticular formation, on both ipsi- and contralateral sides. After wheat germ agglutinin-horseradish peroxidase injections in the associative pulvinar-lateral posterior complex and mediodorsal nucleus of Macaca sylvana, 45-50% of horseradish peroxidase-positive brainstem peribrachial neurons were also choline acetyltransferase-positive. While cells in the medial part of the cholinergic peribrachial area were found to project especially towards the pulvinar-lateral posterior nuclear complex in monkey, the retrograde cell labeling seen after the mediodorsal injection was mostly confined to the lateral part of both dorsal and ventral aspects of the peribrachial area.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Projections of brainstem core cholinergic and non-cholinergic neurons of cat to intralaminar and reticular thalamic nuclei.

We combined the retrograde transport of wheat germ agglutinin conjugated with horseradish peroxidase with choline acetyltransferase immunohistochemistry to study the projections of cholinergic and non-cholinergic neurons of the upper brainstem core to rostral and caudal intralaminar thalamic nuclei, reticular thalamic complex and zona incerta in the cat. After wheat germ agglutinin-horseradish peroxidase injections in the rostral pole of the reticular thalamic nucleus, the distribution and amount of retrogradely labeled brainstem neurons were similar to those found after tracer injection in thalamic relay nuclei (see preceding paper). After wheat germ agglutinin-horseradish peroxidase injections in the caudal intralaminar centrum medianum-parafascicular complex, rostral intralaminar central lateral-paracentral wing, and zona incerta, the numbers of retrogradely labeled brainstem neurons were more than three times higher than those found after injections in thalamic relay nuclei. The larger numbers of horseradish peroxidase-positive brainstem reticular neurons after tracer injections in intralaminar or zona incerta injections results from a more substantial proportion of labeled neurons in the central tegmental field at rostral midbrain (perirubral) levels and in the ventromedial part of the pontine reticular formation, ipsi- and contralaterally to the injection site. Of all retrogradely labeled neurons in the caudal midbrain core at the level of the cholinergic peribrachial area and laterodorsal tegmental nucleus, 45-50% were also choline acetyltransferase-positive after the injections into central lateral-paracentral and reticular nuclei, while only 25% were also choline acetyltransferase-positive after the injection into the centrum medianum-parafascicular complex. These findings are discussed in the light of physiological evidence of brainstem cholinergic mechanisms involved in the blockade of synchronized oscillations and in activation processes of thalamocortical systems.

Animals↗

Thalamic and cortical spindles during early ontogenesis in kittens.

On birth, focal thalamic recordings show sporadic sequences of spindle waves whereas EEG cortical recordings show no trace of spindles. Thalamic spindles are occasionally transferred to the cortex beginning with the 3rd-4th day. On the 8th-9th day, clear-out spindle sequences, with the same patterns as in the adult animal, appear simultaneously in the thalamus and cortex.

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The deafferented reticular thalamic nucleus generates spindle rhythmicity.

The hypothesis that nucleus reticularis thalami (RE) is the generator of spindle rhythmicity during electroencephalogram (EEG) synchronization was tested in acutely prepared cats. Unit discharges and focal waves were extracellularly recorded in the rostral pole of RE nucleus, which was completely disconnected by transections from all other thalamic nuclei. In some experiments, additional transections through corona radiata created a triangular island in which the rostral RE pole survived with the caudate nucleus, putamen, basal forebrain nuclei, prepyriform area, and the adjacent cortex. Similar results were obtained in two types of experiments: brain stem-transected preparations that exhibited spontaneous spindle sequences, and animals under ketamine anesthesia in which transient spindling was repeatedly precipitated during recording by very low doses of a short-acting barbiturate. Both spindle-related rhythms (7- to 16-Hz waves grouped in sequences that recur with a rhythm of 0.1-0.3 Hz) are seen in focal recordings of the deafferented RE nucleus. The presence of spindling rhythmicity in the disconnected RE nucleus contrasts with total absence of spindles in cortical EEG leads and in thalamic recordings behind the transection. Oscillations within the same frequency range as that of spontaneous spindles can be evoked in the deafferented RE nucleus by subcortical white matter stimulation. In deafferented RE cells, the burst structure consists of an initially biphasic acceleration-deceleration pattern, eventually leading to a long-lasting tonic tail. Quantitative group data show that the burst parameters of disconnected RE cells are very similar to those of RE neurons with intact connections. In the deafferented RE nucleus, spike bursts of RE neurons recur periodically (0.1-0.3 Hz) in close time-relation with simultaneously recorded focal spindle sequences. The burst occurrence of deafferented RE cells is greatly reduced after systemic administration of bicuculline. The preservation of both spindle-related rhythms in the disconnected RE nucleus, together with our recent experiments showing abolition of spindle oscillations in thalamic nuclei after lesions of RE nucleus (24), demonstrate that RE nucleus is the generator of spindle rhythms.

Afferent Pathways↗

Physiological characteristics of anterior thalamic nuclei, a group devoid of inputs from reticular thalamic nucleus.

This study tested the hypothesis that neurons of thalamic nuclei, which are normally devoid of inputs from the reticular thalamic nucleus, do not display spindle oscillations and related rhythmic spike bursts. This proposal derived from our recent studies indicating that the reticular nucleus is the generator of spindling rhythmicity. We used retrograde tracing methods, intracellular recordings in barbiturized cats, and extracellular recordings of single neurons and field potentials in anteroventral (AV), anteromedial (AM), ventroanterior (VA), ventrolateral (VL), and central lateral (CL) thalamic nuclei in cats with rostral brain stem transections (cerveau isolé preparations), before and after administration of barbiturates. The observation that AV and AM nuclei do not receive inputs from the reticular nucleus was confirmed by using injections of horseradish peroxidase conjugated to wheat germ agglutinin confined within the limits of anterior nuclei. Such injections led to massive retrograde labeling in mammillary nuclei and layer VI of the retrosplenial cortex but left free of labeling the neurons of the reticular thalamic nucleus. Intracellular recordings showed that AV-AM neurons discharge tonically in response to a depolarizing current applied at rest, whereas they give rise to a slow spike that underlies a burst of fast action potentials when the membrane is hyperpolarized by 5-12 mV. Despite the fact that they share similar properties with other thalamic neurons, intracellularly recorded AV-AM neurons do not exhibit spindle waves under barbiturate anesthesia, whereas VA-VL, CL, and other thalamocortical neurons that receive afferents from the reticular nucleus commonly display such oscillations. With extracellular recordings performed simultaneously in CL and AV or AM nuclei of the unanesthetized cerveau isolé preparation, focal spindle oscillations and related rhythmic high-frequency spike bursts of single CL cells contrasted with absence of spindles and spike bursts in AV or AM neurons. Spindling could be induced in AV-AM nuclei only after administration of barbiturates at doses exceeding 3 mg/kg, and it appeared approximately 35-40 s after the barbiturate effect was detected in the simultaneously recorded CL nucleus. Moreover, the spike bursts that were elicited in AV-AM neurons after barbiturate administration were not temporally related with focal spindles. Since spindle oscillations did not appear intracellularly in AV-AM neurons, the possibility was envisaged that barbiturate-induced spindles were the passive reflection of field potentials actively generated in neighboring thalamic nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Thalamic burst patterns in the naturally sleeping cat: a comparison between cortically projecting and reticularis neurones.

Unit discharges were extracellularly recorded from antidromically identified thalamocortical neurones of ventralis lateralis (v.l.) and centralis lateralis (c.l.) nuclei as well as from reticularis thalami (re.) neurones during wakefulness and electroencephalogram-synchronized sleep of the behaving cat. Various parameters of sleep-related discharge bursts were analysed. Statistical analyses revealed striking similarities between motor relay (v.l.) and intralaminar (c.l.) neurones. More than 60% of bursts consist of three to five spikes at 250-400 Hz. The defining feature of bursts in all cortically projecting neurones is a progressive increase in the duration of successive interspike intervals. As in thalamocortical cells, all re. neurones change their tonic discharges in waking to bursting firing in sleep, regardless of the increased or decreased firing rates from wake to sleep in individual neurones. The bursts of re. neurones are essentially different from those of thalamocortical cells. In re. neurones, burst structure consists of an initial progressive decrease in duration of interspike intervals, followed by an increase in duration of successive intervals, eventually leading to a long-lasting tonic spike train at about 100 Hz. In contrast with bursts of thalamocortical neurones, only 6% of re. bursts are shorter than 50 ms; the total duration of the burst extends between 50 ms and 1.5 s. Population periburst histograms show the beginning of a decline in firing probability about 1.5 s prior to burst onset and an increased firing probability persisting for 300-350 ms after burst onset. The different electrophysiological properties underlying the burst structure of cat's thalamocortical and re. neurones are discussed, with emphasis on dissimilar aspects of re. bursts in unanaesthetized and barbituratized preparations. Various factors that may account for the transition from tonic mode in waking to bursting mode in sleep are envisaged.

Action Potentials↗

Reticularis thalami neurons revisited: activity changes during shifts in states of vigilance.

This study tested the hypothesis that inhibitory actions are exerted by reticularis thalami (RE) neurons upon thalamocortical neurons. The RE neurons were recorded in the rostral pole and lateral districts of the nucleus, and were activated monosynaptically by cortical volleys. Thalamocortical neurons were identified antidromically in intralaminar and ventrolateral nuclei. During sleep with EEG synchronization, prolonged spike barrages of RE neurons extended over the whole spindle sequences. This result suggests that RE neurons are depolarized throughout spindle oscillations, whereas thalamocortical neurons show, simultaneously, long hyperpolarizations and short rebounds. During waking, parallelism rather than reciprocity was found between RE and thalamocortical neurons. Spontaneous discharge rates almost doubled in RE neurons on arousal from sleep, and the probability of cortically evoked short-latency discharges increased. The increase in spontaneous firing rates of RE neurons during natural arousal is consistent with their short-latency synaptic excitation by stimulating the rostral brain stem reticular formation after chronic degeneration of passing fibers. We suggest that RE cells inhibit GABAergic local-circuit cells, in addition to inhibiting thalamocortical neurons, and that different ratios of inhibitory effects are exerted by RE neurons upon these two cell classes during waking and sleep. We further suggest that, upon arousal, disinhibition of thalamocortical neurons (via the local-circuit neurons) outweighs direct inhibition of the thalamocortical neurons.

Animals↗

Dendrodendritic synapses in the cat reticularis thalami nucleus: a structural basis for thalamic spindle synchronization.

Dendrodendritic synapses have been found between the dendrites of reticularis thalami neurons. These synapses were symmetric and the presynaptic element contained pleomorphic vesicles. A few cases of reciprocal dendrodendritic synapses were also observed. Given the morphological features of the synapses and the well-established GABAergic nature of reticularis neurons it is concluded that reticularis cell dendrites form a local inhibitory network. The functional implications of this type of organization for the synchronization of spindle oscillations are discussed and a new hypothesis is proposed.

Animals↗

Absence of spindle oscillations in the cat anterior thalamic nuclei.

Intracellular recordings were performed in cat anterior thalamic nuclei (anterior ventral, medial and dorsal) which, according to a recent anatomical study, do not receive afferents from the reticularis thalami nucleus. Neurons of anterior nuclei did not display spontaneous membrane potential oscillations of the spindle type and such oscillations could neither be evoked in these cells by cortical stimulation. The absence of spontaneous and evoked spindling activity was observed despite that anterior thalamic cells displayed intrinsic membrane properties similar to those of thalamocortical cells in other nuclei. Electrographic recordings from cortical areas connected to anterior thalamic nuclei were also free of spindle activity. Taken together with the evidence that thalamic relay neurons deprived from their reticularis input by sections or kainic acid lesions lose their spindling activity, our results point to the essential role of the reticularis complex in the genesis of thalamic spindle waves.

Animals↗

The effects of QX314 on thalamic neurons.

The effects of QX314 were studied in cat thalamic neurons recorded in vivo. Besides blocking Na+ spike electrogenesis, QX314 transformed spindle oscillations into a single long-lasting period of hyperpolarization that terminated with a rebound Ca2+ spike. Large sustained injections of the drug resulted in the occurrence of numerous fast prepotentials that had the characteristics of attenuated dendritic Ca2+ spikes. These effects are interpreted as resulting from the blockage by QX314 of a persistent Na+ current and a delayed rectifier K+ current which currents have already been disclosed in thalamic neurons recorded in vitro.

Animals↗

Abolition of spindle oscillations in thalamic neurons disconnected from nucleus reticularis thalami.

The effects of depriving thalamic relay and intralaminar nuclei from their reticularis thalami (RE) inputs were investigated in acute and chronic experiments on cat. In acutely prepared animals, two (frontal and parasagittal) thalamic transections were made; extracellular and intracellular recordings were performed in RE-disconnected thalamic nuclei. In chronic experiments, the RE nuclear complex was lesioned by means of kainic acid injections; the activity of RE-deprived thalamocortical neurons was extracellularly studied during wakefulness and synchronized sleep. Two features distinguish RE-deprived nuclei from normal thalamic nuclei: absence of spindle-wave rhythmicity and all-burst activity of neurons. The abolition of spindle-related rhythms (sequences of 7- to 14-Hz waves recurring periodically with a rhythm of 0.1-0.2 Hz) in RE-disconnected thalamic nuclei and ipsilateral neocortical areas contrasted with normal spindling rhythmicity in contralateral EEG leads. Spontaneously occurring, rhythmic, long-lasting inhibitory postsynaptic potentials (IPSPs), as observed in intact preparations, were no longer observed in RE-disconnected thalamic neurons. The remaining inhibitory events consisted of short-duration IPSPs. The possibility that RE nucleus is a pacemaker for spindling rhythms, imposing them through inhibitory projections to target thalamic areas, is supported by our concurrent experiments that indicate RE neurons preserve their rhythmicity after disconnection from their major (cortical and thalamic) input sources. RE-deprived thalamocortical neurons exclusively exhibit high-frequency spike bursts whose intrinsic structure is identical to that of intact thalamic relay cells. Instead of the spindle-related sequences of bursts seen in normal animals, the bursts of RE-disconnected thalamocortical neurons are single events, with a dramatic rhythmicity at 1-2 Hz. The presumed mechanism of this rhythmicity is the periodic activation of a low-threshold somatic conductance whose deinactivation is brought about by temporal integration of short-lasting IPSPs. It is known that high-frequency spike bursts of thalamic relay neurons result from hyperpolarization of cell membrane. We blocked the underlying inhibitory events by bicuculline and reversibly changed the all-burst activity of RE-disconnected neurons into a tonic mode. Since the only activity of RE-deprived thalamocortical neurons consists of burst discharges, we hypothesize that local-circuit GABAergic neurons are released from inhibition after RE disconnection or lesion.

Action Potentials↗

Thalamic projections of nucleus reticularis thalami of cat: a study using retrograde transport of horseradish peroxidase and fluorescent tracers.

The retrograde transport of horseradish peroxidase (HRP) and fluorescent tracers after injections in various thalamic nuclei was used to investigate the relative density of retrogradely labeled cells in different districts of reticularis thalami (RE) nuclear complex of cat. The RE nucleus was left virtually free of labeling only after injections localized into the anterior nuclear group; in those experiments, heavy retrograde labeling was obtained in mammillary nuclei. The major targets of RE cells proved to be centralis lateralis-paracentralis (CL-PC) and centrum medianum-parafascicularis (CM-PF) intralaminar nuclei. The projections to various intralaminar nuclei mainly arise in the rostral pole and rostrolateral part of RE nucleus and are reciprocal to intralaminar-RE pathways disclosed by Jones ('75). The RE territories labeled following injections in relay and associational nuclei are more restricted and are located contiguously and slightly anteriorly to a given nucleus. There was a very small proportion of doubly labeled RE cells after injections with fluorescent tracers in different nuclei. This was not due to a technical failure since many double-labeled neurons were found in the same material in medial globus pallidum after thalamic and midbrain injections (see companion paper by Parent and Steriade, '84). We conclude that most individual RE axons arborize in only one thalamic nucleus or nuclear group. An additional finding was the existence of intralaminar-to-relay (CL-PC to VA-VL) projections.

Animals↗