Iodine Extravasation Quantification on Dual-Energy CT of the Brain Performed after Mechanical Thrombectomy for Acute Ischemic Stroke Can Predict Hemorrhagic Complications.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents a potentially severe complication of revascularization of acute ischemic stroke. The aim of our study was to assess the capability of iodine extravasation quantification on dual-energy CT performed immediately after mechanical thrombectomy to predict hemorrhagic complications. MATERIALS AND METHODS: Because this was a retrospective study, the need for informed consent was waived. Eighty-five consecutive patients who underwent brain dual-energy CT immediately after mechanical thrombectomy for acute ischemic stroke between August 2013 and January 2017 were included. Two radiologists independently evaluated dual-energy CT images for the presence of parenchymal hyperdensity, iodine extravasation, and hemorrhage. Maximum iodine concentration was measured. Follow-up CT examinations performed until patient discharge were reviewed for intracerebral hemorrhage development. The correlation between dual-energy CT parameters and intracerebral hemorrhage development was analyzed by the Mann-Whitney U test and Fisher exact test. Receiver operating characteristic curves were generated for continuous variables. RESULTS: Thirteen of 85 patients (15.3%) developed hemorrhage. On postoperative dual-energy CT, parenchymal hyperdensities and iodine extravasation were present in 100% of the patients who developed intracerebral hemorrhage and in 56.3% of the patients who did not (P = .002 for both). Signs of bleeding were present in 35.7% of the patients who developed intracerebral hemorrhage and in none of the patients who did not (P < .001). Median maximum iodine concentration was 2.63 mg/mL in the patients who developed intracerebral hemorrhage and 1.4 mg/mL in the patients who did not (P < .001). Maximum iodine concentration showed an area under the curve of 0.89 for identifying patients developing intracerebral hemorrhage. CONCLUSIONS: The presence of parenchymal hyperdensity with a maximum iodine concentration of >1.35 mg/mL may identify patients developing intracerebral hemorrhage with 100% sensitivity and 67.6% specificity.

Rolling and adhesion of human tumor cells on vascular endothelium under physiological flow conditions.

We investigated the interaction of different human tumor types with resting and IL-1-activated human umbilical vein endothelial cells under laminar flow conditions using a parallel plate flow chamber. Three tumor cell lines (the HT-29M colon carcinoma, the OVCAR-3 ovarian carcinoma, and the T-47D breast carcinoma) showed limited adhesion to unstimulated endothelial cells at any of the shear stress levels tested, while rolling and massive adhesion of tumor cells were observed on IL-1-activated endothelial cells. Three other tumor cell lines (the A375M and A2058 melanomas and the MG-63 osteosarcoma) did not adhere on resting endothelial cells at high shear stress (> 1.5 dyn/cm2) and started to adhere with decreasing shear stress; the number of adherent cells increased steeply on IL-1-activated endothelial cells, but no cell rolling was observed even at the highest shear stress. These mechanisms of tumor cell interaction with endothelial cells were analyzed in detail using the HT-29M colon carcinoma and the A375M melanoma. Incubation of activated endothelial cells with a monoclonal antibody against E-selectin inhibited rolling and adhesion of HT-29M, but had no effect on the adhesion of A375M cells; monoclonal antibody against vascular cell adhesion molecule-1 reduced the adhesion of A375M cells and had no effect on HT-29M. The selective interaction of these two molecules with tumor cells was confirmed by measuring the adhesion of tumor cells on immobilized soluble proteins. On E-selectin-coated surfaces, HT-29M cells rolled during perfusion experiments without subsequent adhesion, while A375M cells did not adhere. On vascular cell adhesion molecule-1-coated surfaces, HT-29M cells neither adhered nor rolled, while A375M cells adhered massively without rolling. Under flow conditions, therefore, cells from different tumor types interact with the endothelial surface by different mechanisms, depending on adhesion molecules expressed on the tumor and endothelial cell surface.

Phenotypic and functional characteristics of tumour-derived microvascular endothelial cells.

We recently developed a method for the isolation and purification of tumour-derived endothelium. In this study the phenotypic and functional properties of human tumour-derived microvascular endothelial cells (TdMEC) were examined. Endothelium obtained from human adrenal gland specimens (HAMEC) was used as a reference microvascular endothelial cell population. TdMEC formed a confluent monolayer with the typical morphological appearance of endothelium and were positive for endothelial markers such as Ulex-1 lectin, CD31 antigen, von Willebrand Factor and VE-cadherin. The addition of acidic Fibroblast Growth Factor (aFGF), basic FGF (bFGF) or Vascular Endothelial Growth Factor (VEGF) substantially improved proliferation of TdMEC; and kidney carcinoma derived endothelial cells were more responsive to FGFs, whereas glioblastoma derived endothelial cells greatly responded to VEGF TdMEC expressed high levels of the VEGF receptors, KDR/flk-1 and Flt-1, as shown by northern blot analysis. TdMEC expressed the adhesion molecules ICAM-1, VCAM-1 and E-selectin that could be further increased by exposing TdMEC culture to interleukin-1. All the TdMEC expressed interleukin-8 mRNA. These findings show that TdMEC in vitro maintain several of the features described for microvasculature. Thus, TdMEC represent a useful tool to study markers for tumor vasculature.

Various types of inhibitory postsynaptic potentials in anterior thalamic cells are differentially altered by stimulation of laterodorsal tegmental cholinergic nucleus.

The effects of stimulating the laterodorsal tegmental cholinergic nucleus upon inhibitory postsynaptic potentials recorded in relay cells of the anterior thalamic complex were studied in urethane-anesthetized cats. The inhibitory postsynaptic potentials induced in anterior thalamic relay cells by stimulating mammillary nuclei or retrosplenial cortex are generated by local-circuit inhibitory neurons since this nuclear complex is devoid of afferents from the other intrathalamic source of inhibition, the reticular thalamic nucleus. In a parallel study from this laboratory, it has been shown that cortical stimulation elicits a biphasic inhibitory postsynaptic potential consisting of two (A and B) components attributed to axonal firing of local interneurons, whereas mammillary stimulation elicits, in addition to the A-B sequence, an earlier component (a) presumably generated by presynaptic dendrites in thalamic glomeruli. In the present study, short pulse-trains applied to the laterodorsal tegmental nucleus diminished the amplitudes of A and B inhibitory components or completely suppressed them. The B component was more sensitive to the depressive effect. By contrast with the changes of the A and B components, the mammillary-evoked a inhibitory component was not reduced and, in many instances, was enhanced following laterodorsal tegmental stimulation. The effects of laterodorsal tegmental stimulation survived monoamine depletion by reserpine. We suggest that mesopontine cholinergic depressive actions on A and B inhibitory postsynaptic potentials may be due to an increased conductance in thalamocortical cells during the short-lasting nicotinic action combined with a somatic hyperpolarization of local-circuit cells, whereas the enhancement of the earliest (a) inhibitory postsynaptic potential reflects a concomitant potentiating action at the level of intraglomerular presynaptic dendrites.

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

Thalamocortical neurons located in the large-celled district of the cat intralaminar centrolateral nucleus were found to discharge spike-bursts with unusually high frequencies (800-1000 Hz) during spindle oscillations of the electroencephalogram. In chronically implanted animals, similar spike-bursts were also fired during wakefulness and rapid eye movement sleep, two behavioral states in which other thalamocortical neurons tonically fire single spikes. Such high-frequency spike-bursts recurred with a fast rhythm of 20-40 Hz during waking and rapid eye movement sleep. Intracellular recordings under barbiturate anesthesia showed that, during spindle oscillations, the spike-bursts of intralaminar neurons are generated by brief low-threshold spikes with a much shorter refractory phase than in other thalamocortical cells. Depolarizing pulses from the resting membrane potential triggered fast oscillations (20-80 Hz) crowned by short high-frequency (800-1000 Hz) spike-bursts. During the inter-spindle epochs, the "tonic" firing of these neurons was, in fact, a fast oscillation (30-40 Hz) of the membrane potential leading to single spikes or spike-doublets. Autocorrelograms computed from inter-spindle epochs, at relatively depolarized levels, confirmed the presence of multiple peaks at this fast rhythm. The properties of these neurons make them well suited for the distribution of fast rhythms during arousal and rapid eye movement sleep over the cerebral cortex.

Intracellular evidence for incompatibility between spindle and delta oscillations in thalamocortical neurons of cat.

Recent studies have revealed that the thalamus does not only generate spindle oscillations (7-14 Hz), but that it also participates in the genesis of a slower (less than 4 Hz) rhythm within the frequency range of delta waves on the electroencephalogram. In thalamic cells, delta is an intrinsic oscillation consisting of low-threshold spikes alternating with afterhyperpolarizing potentials. It is known from electroencephalographic recordings in humans and animals that slow or delta waves prevail during late sleep stages, whereas spindle oscillations are characteristic for the early stages of sleep. We studied the dependence of spindles and delta oscillations on membrane potential, as well as the effects of spindles on delta oscillations, in thalamocortical neurons of cats under urethane anesthesia and in cerveau isolé preparations (low collicular transections). Spindles appeared at membrane potentials between -55 and -65 mV, whereas delta oscillations occurred by bringing the membrane potential between -68 and -90 mV. Spindles either evoked by cortical stimulation or occurring spontaneously in cerveau isolé preparations prevented delta oscillations. This effect was probably due to the increase in membrane conductance associated with spindles. Barbiturates also blocked delta activity in thalamocortical neurons, probably through the same mechanism. A certain degree of incompatibility between spindles and delta rhythms in thalamocortical cells may explain the prevalence of these two types of oscillations during different stages of sleep with synchronization of the electroencephalogram.

Substantia nigra reticulata neurons during sleep-waking states: relation with ponto-geniculo-occipital waves.

We have previously hypothesized that the spike bursts of brainstem peribrachial (PB) neurons, leading to ponto-geniculo-occipital (PGO) waves in thalamocortical systems, are triggered by phasic hyperpolarizations of sufficient magnitude or by excitatory inputs reaching a steadily hyperpolarized membrane. We have proposed that the source of these hyperpolarizing actions are substantia nigra pars reticulata (SNr) cells that project to, and exert inhibitory effects upon, PB neurons. Here we tested this hypothesis by recording antidromically identified SNr-PB cells in chronically implanted, naturally sleeping cats. A subpopulation of SNr-PB cells exhibited tonically increased firing preceding by 70-200 ms the thalamic PGO wave. These data support the hypothesis that an enhancement in SNr-cells' discharges may lead to hyperpolarization of PB neurons, with the consequence of spike bursts in one class of PGO-related PB-thalamic neurons.

Ethosuximide alters intrathalamic and thalamocortical synchronizing mechanisms: a possible explanation of its antiabsence effect.

Effects of systemic administration of a single dose (50 mg/kg) of ethosuximide (ESM) on extracellularly recorded thalamic (nucleus centralis lateralis, CL; nucleus reticularis, RE) and cortical neurons and on cortical EEG activity of acute cats, have been studied. In intact animals ESM led to: (a) desynchronization of cortical EEG activity; (b) reduction of cortical recruiting responses to 6 Hz stimulation of nucleus centralis medialis (CeM); (c) increased firing rate of CL units; and (d) reduction of incremental responses (IRs) of CL neurons to CeM stimulation. In midbrain reticular formation (MRF)-lesioned animals, ESM induced: (a) reduction of cortical spindle waves; (b) increment of their intraburst frequency; (c) reduction of the IR of CL neurons to 3 and 6 Hz CeM stimulation; (d) shortening of the inhibitory period following each response; and (e) no increment of spontaneous firing rate of CL units. Moreover, ESM led to important changes in the spontaneous activity of RE neurons: spike barrages, typical of these neurons in MRF-lesioned animals, became less frequent and of longer duration, being also constituted by longer interspike intervals. However, responses of RE neurons to low frequency CeM stimulation, when present, did not show any incremental phenomenon and appeared unchanged after ESM. Responses of cortical neurons to paired stimuli, applied with different interstimulus intervals, to nucleus ventralis posterolateralis or in animals with isolated cortex, to subcortical white matter, disclosed a reduction of the cortical inhibitory period following the response to the conditioning stimulus. These data suggest that ESM exerts a moderate diffuse anti-inhibitory action at both cortical and thalamic levels and an activating effect on MRF, which could also be accomplished through disinhibition. The reduction of the inhibitory phases in thalamic nuclei would alter spontaneous intrathalamic synchronizing mechanisms, leading to a decreased effectiveness of thalamocortical volleys, which are believed to be fundamental for the appearance of cortical spike and wave discharges. This hypothesis would therefore explain the specific efficacy of ESM against absence seizures.

Kriss cuts for the correction of high myopia.

We describe a radial keratotomy technique for the correction of high myopia. At present, the highest myopic correction is obtained by the smallest optical zone diameter (3 mm), by the maximum number of incisions (16), by the maximum number of redeepenings (3), and by incision of the tissue bridges. To obtain additional corneal flattening, we suggest lengthening the incisions curvilinearly. We present results of cases treated with curvilinear incision and two other techniques.

Characterization of novel clonal murine endothelial cell lines with an extended life span.

A murine endothelial cell line was recently established from microvessels that had invaded a subcutaneous sponge implant (Dong, Q. G.; Bernasconi, S.; Lostaglio, S., et al. Arterioscl. Thromb. Vasc. Biol. 17:1599-1604; 1997). From these sponge-induced endothelial (SIE) cells, we have isolated two subpopulations endowed with different phenotypic properties. Clone SIE-F consists of large, highly spread cells that have a relatively slow growth rate, form contact-inhibited monolayers, do not grow under anchorage-independent conditions, express elevated levels of thrombospondin-1 (TSP-1) and are not tumorigenic in vivo. In contrast, clone SIE-S2 consists of small, spindle-shaped cells that have a high proliferation rate, do not show contact-inhibition, grow under anchorage-independent conditions, express very low levels of TSP-1 and are tumorigenic in vivo. Both clones express the endothelial markers vascular endothelial-cadherin and vascular intercellular adhesion molecule-1, but do not express CD31 and E-selectin. In addition, SIE-S2 cells, but not SIE-F cells, express the alpha-smooth muscle actin isoform. SIE-S2 cells, but not SIE-F cells, are able to form branching tubes in fibrin gels. The SIE-F and SIE-S2 clones, which have properties of nontransformed and transformed cells, respectively, should provide useful tools to investigate physiological and pathological processes involving vascular endothelium.

Extracorporeal lung perfusion and ventilation to improve donor lung function and increase the number of organs available for transplantation.

INTRODUCTION: Ex vivo lung perfusion (EVLP) has been validated as a valuable technique to increase the pool of organs available for lung transplantation. MATERIAL AND METHODS: After a preclinical experience, we obtained permission from the Ethics Committee of our institution to transplant lungs after EVLP reconditioning. ABO compatibility, size match, and donor arterial oxygen pressure (PaO(2))/fraction of inspired oxygen (FiO(2)) ≤ 300 mm Hg were considered to be inclusion criteria, whereas the presence of chest trauma and lung contusion, evidence of gastric content aspiration, pneumonia, sepsis, or systemic disease were exclusion criteria. We only considered subjects on an extra corporeal membrane oxygenation (ECMO) bridge to transplantation with rapid functional deterioration. Using Steen solution with packed red blood cells oxygenated with 21% O(2), 5% to 7% CO(2) was delivered, targeted with a blood flow of approximately 40% predicted cardiac output. Once normothermic, the lungs were ventilated with a tidal volume of 7 mL/kg a PEEP of 5 cmH(2)O and a respiratory rate of 7 bpm. Lungs were considered to be suitable for transplantation if well oxygenated [P(v-a) O(2) > 350 mm Hg on FiO(2) 100%], in the absence of deterioration of pulmonary vascular resistance and lung mechanics over the perfusion time. RESULTS: From March to September 2011, six lung transplantations were performed, including two with EVLP. The functional outcomes were similar between groups: at T72 posttransplantation, the median PaO(2)/FiO(2) were 306 mm Hg (range, 282 to 331 mm Hg) and 323 mm Hg (range, 270 to 396 mm Hg) (P = 1, EVLP versus conventional). Intensive care unit ICU and hospital length of stay were similar (P = .533 and P = .663, respectively) with no mortality at 60 days in both groups. EVLP donors were older (49 ± 6 y versus 21 ± 7 y, P < .05), less well oxygenated (184 ± 6 mm Hg versus 570 ± 30, P < .05), displaying higher Oto scores (9.5 ± 0.7 versus 1.7 ± 1.5, P < .05). CONCLUSIONS: The first 6 months of the EVLP program allowed us to increase the number of organs available for transplantation with short-term outcomes comparable to conventional transplantations.

[Automatic recognition of spike-wave discharges in dynamic EEG]. / Riconoscimento automatico delle scariche punta-onda nell'EEG dinamico.

A computerized system for automatic recognition of spike and wave discharges (SWDs), recorded by ambulatory EEG, is described. Four parameters were sequentially considered for detecting SWDs: amplitude, frequency, rhythmicity and second derivative of the EEG epochs to be evaluated. With this system the computer was able to recognize in 20 patients 95% +/- 4.7 of SWDs visually detected, while the percentage of the SWDs as compared with the total number of "discharges" found by the computer was 82.4% +/- 15.5.

[Convulsive episodes caused by a suspension of lorazepam]. / Episodi convulsivi da sospensione di lorazepam.

Seven cases of convulsive seizure occurring after abrupt withdrawal of Lorazepam in non epileptic patients are reported. Five ot of them had an important cerebral damage occurred in perinatal period. All patients, before withdrawal, had been taking Lorazepam, 5-15 mg/day, for at least six months. It is stressed that in similar cases there is no need to start an anticonvulsive therapy because usually there is not a spontaneous recurrence of convulsive seizures. It is suggested that withdrawal of long term treatments with high doses of benzodiazepines be accomplished carefully and very slowly especially in patients with a previous cerebral damage.

Bursting and tonic discharges in two classes of reticular thalamic neurons.

1. Two types of cat reticular (RE) thalamic cells were disclosed by means of intracellular recordings under urethan anesthesia. The RE neurons were identified by their typical depolarizing spindle oscillations in response to synchronous stimulation of the internal capsule. 2. In type I neurons (n = 41), depolarizing current pulses induced tonic firing at the resting or slightly depolarized membrane potential (Vm) and triggered high-frequency spike bursts at a Vm more negative than -75 mV. As well, these cells discharged rebound bursts at the break of a hyperpolarizing current pulse. Internal capsule stimulation elicited spindle sequences made off by depolarizing waves giving rise to spike bursts. 3. Type II cells (n = 9) did not discharge spike bursts to large depolarizing current pulses even when the Vm reached -100 mV, nor did they fire rebound bursts after long-lasting hyperpolarizing current pulses or spike bursts riding on the rhythmic depolarizing components of spindle sequences. 4. Compared with type I cells, type II cells showed less frequency accommodation during tonic firing. The latter neuronal class discharged at high frequencies (40 Hz) with slight DC depolarization, approximately 8-10 Hz at the resting Vm, and no underlying synaptic or subthreshold oscillatory events could be detected when the firing was blocked by DC hyperpolarization. 5. The presence of two cell classes in the RE nucleus challenges the common view that this nucleus consists of a single neuronal class. We suggest that a different set of conductances is present in type II RE neurons, thus preventing the low-threshold Ca2+ current from dominating the behavior of these cells.

Electrophysiology of a slow (0.5-4 Hz) intrinsic oscillation of cat thalamocortical neurones in vivo.

1. Electrophysiologically identified thalamocortical neurones have been intra- and extracellularly recorded in acutely prepared cats, under different anaesthetic conditions. 2. A slow (0.5-4 Hz) membrane potential oscillation was observed in thalamocortical cells recorded in motor, sensory, associational and intralaminar thalamic nuclei. The oscillation consisted of rhythmic low-threshold spikes alternating with after-hyperpolarizations. 3. About 80% of the neurones with intact cortical connections were set into the slow oscillatory mode by bringing their membrane potential to between -68 and -90 mV. The oscillation did not depend upon the occurrence of fast action potentials and did not outlast the imposed hyperpolarization. 4. Anatomical or functional disconnection from related cortical areas resulted in a membrane potential hyperpolarization of about 9 mV and in the occurrence of spontaneous slow oscillations in virtually all recorded neurones. The intrinsic nature of the phenomenon was supported by the lack of rhythmic postsynaptic potentials as the cells were prevented from oscillating by outward current injection. 5. In contrast with other thalamic nuclei, the slow oscillation has not been observed in anterior thalamic neurones despite their having similar basic electrophysiological properties. 6. Barbiturate administration suppressed the slow oscillatory mode, an effect accompanied by a decrease in the membrane input resistance. 7. Multiunit recordings of spontaneously oscillating cells showed epochs characterized by phase-related firing. This synchronous discharge was paralleled by a clear-cut build-up of field potentials in the frequency range of electroencephalogram slow or delta waves. 8. These results demonstrate that the majority of thalamocortical neurones are endowed with electrophysiological properties allowing them to oscillate at 0.5-4 Hz, if they have a membrane potential more negative than -65 mV and a high input resistance. Such a condition is physiologically achieved in the deepest stages of electroencephalogram-synchronized sleep, as a result of brain stem-thalamic as well as cortico-thalamic deafferentation. We postulate a thalamic contribution in the genesis of electroencephalogram delta waves during slow wave sleep, once independently oscillating thalamocortical cells become in phase.

Brainstem genesis of reserpine-induced ponto-geniculo-occipital waves: an electrophysiological and morphological investigation.

Several experimental results indicate that the peribrachial (PB) cholinergic area of the pedunculopontine nucleus is the final relay for the transfer of brainstem-generated pontogeniculo-occipital (PGO) waves to the thalamus. However, the mechanisms underlying the PGO-related activity of PB neurons remain unknown. In order to study these mechanisms, single unit recordings in the PB area were performed in reserpinized cats. Because PGO waves are closely related to rapid eye movements, our microelectrode explorations were also aimed to some structures of the preoculomotor network, namely, the superior colliculus (SC) and parts of the central tegmental field (FTC). We have found several classes of PGO-on cells in the PB area, most of them descharging 80 ms or less before the peak of PGO waves. These cell-classes comprised high-frequency bursting cells, slow-frequency bursting cells, and neurons discharging single spikes or doublets. Intracellular recordings showed that PGO-on single spikes arise from conventional excitatory postsynaptic potentials. Among PGO-related cells in structures outside the PB limits, it was found that most SC cells discharge during or after the PGO, whereas FTC cells increase their discharge rate several hundreds of ms before PGO waves, thus indicating that PGO waves are elaborated long before the activation of PB neurons. Massive retrograde labeling was found in FTC following horseradish peroxidase injections into the PB area. We suggest that long-lead FTC neurons provide an excitatory input to PGO-on PB neurons.

Three types of inhibitory postsynaptic potentials generated by interneurons in the anterior thalamic complex of cat.

1. These experiments were carried out to study how thalamic interneurons generate inhibitory postsynaptic potentials (IPSPs) in relay cells. Intracellular recordings were performed in the anterior thalamic (AT) nuclei, a nuclear group in which interneurons constitute the only intrathalamic source of gamma-aminobutyric acid (GABA). 2. In the AT complex, as in most dorsal thalamic nuclei, interneurons can influence relay cells through their presynaptic dendrites (PSDs) and their axons. This dual mode of action is paralleled by a different termination pattern of prethalamic fibers and cortical axons on interneurons. Prethalamic fibers, which in the AT nuclei arise in the mammillary bodies (MBs), end mostly on PSDs, whereas cortical terminals usually synapse on the parent dendrites of PSDs. We therefore took advantage of the differential mode of termination of cortical and MB afferents on interneurons to infer the respective roles of the axons and PSDs of interneurons in the genesis of the IPSPs recorded from relay cells. 3. In all responsive AT cells, cortical stimuli delivered at low frequency (less than or equal to 0.5 Hz) evoked a biphasic IPSP, with an early and a late phase, having a total duration of 221.96 +/- 8.18 ms (mean +/- SE). The early part of the IPSP (termed A) had a reversal potential (ER) close to the equilibrium potential for Cl- ions: -79.25 +/- 2.14 mV. Furthermore, it reversed in polarity after impalement of the cells with KCl-filled pipettes. The late IPSP (termed B) always began before the end of the early IPSP, 45.93 +/- 2.50 ms after the onset of the A-IPSP. The B-IPSP had an ER of -109 +/- 2.4 mV and was not affected by Cl- injection. 4. By contrast, MB stimuli delivered at low frequency (less than or equal to 0.5 Hz) evoked a triphasic IPSP having a total duration of 220.5 +/- 9.42 ms in most (61.2%) AT cells. The IPSP with the shortest latency (termed a) was evoked only by MB stimuli. Before the return of the membrane potential to the resting level, a second hyperpolarizing potential began (7.41 +/- 0.46 ms after the onset of the a-IPSP). This second inhibitory phase was biphasic and had electrophysiological characteristics similar to the biphasic A- and B-IPSP evoked by cortical stimulation. Both the MB-evoked a- and A-IPSPs had an ER close to the equilibrium potential for Cl- ions (-72.22 +/- 0.68 and -72 +/- 0.82 mV, respectively) and reversed in polarity after impalement of the cells with KCl-filled pipettes.(ABSTRACT TRUNCATED AT 400 WORDS)

Network modulation of a slow intrinsic oscillation of cat thalamocortical neurons implicated in sleep delta waves: cortically induced synchronization and brainstem cholinergic suppression.

A slow (0.5-4 Hz) oscillation of thalamic neurons was recently described and attributed to the interplay of two intrinsic currents. In this study, we investigated the network modulation of this intrinsic thalamic oscillation within the frequency range of EEG sleep delta-waves. We performed intracellular and extracellular recordings of antidromically identified thalamocortical cells (n = 305) in sensory, motor, associational, and intralaminar nuclei of anesthetized cats. At the resting membrane potential, Vm (-60.3 +/- 0.4 mV, mean +/- SE), cortical stimulation induced spindle-like oscillations (7-14 Hz), whereas at Vm more negative than -65 mV the same stimuli triggered an oscillation within the EEG delta-frequency (0.5-4 Hz), consisting of low-threshold spikes (LTSs) followed by after hyperpolarizing potentials (AHPs). The LTS-AHP sequences outlasted cortical stimuli as a self-sustained rhythmicity at 1-2 Hz. Corticothalamic stimuli were able to transform subthreshold slow (0.5-4 Hz) oscillations, occurring spontaneously at Vm more negative than -65 mV, into rhythmic LTSs crowned by bursts of Na+ spikes that persisted for 10-20 sec after cessation of cortical volleys. Cortical volleys also revived a hyperpolarization-activated slow oscillation when it dampened after a few cycles. Auto- and crosscorrelograms of neuronal pairs revealed that unrelated cells became synchronized after a series of corticothalamic stimuli, with both neurons displaying rhythmic (1-2 Hz) bursts or spike trains. Since delta-thalamic oscillations, prevailing during late sleep stages, are triggered at more negative Vm than spindles characterizing the early sleep stage, we postulate a progressive hyperpolarization of thalamocortical neurons with the deepening of the behavioral state of EEG-synchronized sleep. In view of the evidence that cortical-elicited slow oscillations depend on synaptically induced hyperpolarization of thalamocortical cells, we propose that the potentiating influence of the corticothalamic input results from the engagement of two GABAergic thalamic cell classes, reticular and local-circuit neurons. The thalamocorticothalamic loop would transfer the spike bursts of thalamic oscillating cells to cortical targets, which in turn would reinforce the oscillation by direct pathways and/or indirect projections relayed by reticular and local-circuit thalamic cells. Stimulation of mesopontine cholinergic [peribrachial (PB) and laterodorsal tegmental (LDT)] nuclei in monoamine-depleted animals had an effect that was opposite to that exerted by corticothalamic volleys. PB/LDT stimulation reduced or suppressed the slow (1-4 Hz) oscillatory bursts of high-frequency spikes in thalamic cells.(ABSTRACT TRUNCATED AT 400 WORDS)