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The acute pretrigeminal rat.

In five rats the brainstem was transected at the pretrigeminal level. In the frontal cortex, desynchronized EEG activity dominated, while in the dorsal hippocampus theta activity of low frequency (about 4 cycle/s) was almost continuously present. Olfactory and visual stimuli and electrical stimulation of the posterior hypothalamus induced or increased cortical EEG desynchronization and increased the regularity and the frequency of the theta activity in the hippocampus. However, visual stimuli were effective only in three rats. Ocular responses (pupillary dilatation, eye movements) were never observed to any stimulation. It is suggested that similarly as in the pretrigeminal cat, the isolated cerebrum is awake in the pretrigeminal rat.

Animals↗

Action potentials and release of neurohypophysial hormones in vitro.

1. Isolated rat neurohypophyses were studied in vitro and the hormones released on electrical stimulation of the pituitary stalk or on exposure to excess potassium were estimated by a milk-ejection assay.2. The stalk was stimulated with trains of 500 stimuli, or multiples thereof, applied at different frequencies. Below frequencies of ca. 35 c/s, hormone release was found to depend on the total number of stimuli applied as well as on the frequency of stimulation. Above ca. 35 c/s, identical numbers of stimuli were progressively less effective as the frequency of stimulation was increased, and the dependence of the hormone output on the total number of stimuli was less apparent.3. The amplitude of the compound action potential recorded from the neurohypophysis following electrical stimulation of the stalk was found to decrease as a function of the frequency of stimulation. Stimulation at 50 c/s reduced its amplitude about sevenfold within 30 sec.4. The addition of tetrodotoxin (TTX) to the incubation media abolished the compound action potential recorded from the neural lobe as well as the release of hormones evoked by electrical stimulation. Resting release, however, was unaffected by TTX.5. In TTX-treated neural lobes, excess potassium was still effective in eliciting graded secretory responses. This indicates the independence of the release process from the action potential generating mechanism and suggests that TTX-paralysed preparations represent a useful model for the study of hormone release in the absence of conducted action potentials.6. The release of hormones from the neurohypophysis and the release of neurotransmitters at chemical synapses both depend on the entry of calcium into the nerve terminals following their depolarization by invading action potentials. In both systems, experimental separation of the release mechanism can be achieved by the use of TTX. These and other parallels suggest that the release process is similar.

Action Potentials↗

Post-tetanic burst: a new monitoring method for intense neuromuscular block.

A new stimulation pattern for evaluation of intense neuromuscular block (post-tetanic burst (PTB)) was compared with post-tetanic twitch (PTT) during spontaneous recovery from vecuronium-induced neuromuscular block. Thirty adult patients were allocated to two equal groups and we measured times from administration of vecuronium 0.1 mg kg-1 to return of PTB and PTT responses, and evoked responses to PTB and PTT stimuli. For PTB stimulation, a 50-Hz tetanus was applied at 50 mA for 5 s, and after a pause of 3 s, a 50-Hz burst stimulation was applied, consisting of three impulses at 50 mA. PTB stimuli were delivered every 5 min. Similarly, PTT consisted of a tetanus, a 3-s pause and one single twitch stimulation repeated every 5 min. Time to return of the PTB response was significantly shorter than that of PTT (mean 23.7 (SD 7.9) compared with 30.7 (7.0) min) (P = 0.0160), although evoked responses to PTB did not differ significantly from those of PTT throughout recovery from vecuronium-induced neuromuscular block. This study suggested that PTB was more sensitive in evaluating intense neuromuscular block than PTT.

Adult↗

Detection by in situ hybridization and phenotypic characterization of cells expressing IL-6 mRNA in human stimulated blood.

IL-6 has manifold biologic functions in immune and inflammatory responses and is produced by a variety type of cells. In this work, we used the whole blood culture to identify the cells expressing IL-6 gene/protein after various stimulation. When the whole blood was incubated with LPS or Con A, much IL-6 activity, measured by the growth promoting assay using a murine IL-6-dependent hybridoma clone, was detected in the plasma as early as 4 h of culture and continued to increase with time, reaching a plateau around 12 h. Immunocytochemical analysis with anti-rIL-6 antiserum revealed that a proportion of mononuclear cells (MNC) contained intracytoplasmic IL-6 in LPS- or Con A-stimulated blood. Northern blot analysis for MNC from the blood stimulated with these stimuli showed that their transcripts for IL-6 peaked at 4 h, then rapidly declined and was undetectable after 24 h of stimulation. In situ hybridization technique with radiolabeled antisense RNA probe for IL-6 demonstrated that a fraction of MNC from LPS- as well as Con A-stimulated blood expressed IL-6 mRNA. With the combined use of in situ hybridization and immunofluorescence by corresponding mAb, it was confirmed that IL-6 mRNA expressing cells in stimulated blood were exclusively monocytes. In the whole blood culture, it was shown that expression of IL-6 mRNA by monocytes was inhibited by dexamethasone, but not by cyclosporin A. These results suggest that monocytes are the major cells expressing IL-6 gene/protein in the circulation after exposure to external stimuli.

Antigens, CD↗

Reflex seizures and reflex epilepsy.

Reflex seizures are evoked by a specific afferent stimulus or by activity of the patient and are divided into those characterized by generalized seizures and those principally manifested by focal seizures. Reflex epilepsies are syndromes in which all epileptic seizures are precipitated by sensory stimuli. Three categories of reflex seizures encountered clinically include pure reflex epilepsies, reflex seizures that occur in generalized or focal epilepsy syndromes that are also associated with spontaneous seizures, and isolated reflex seizures occurring in situations that do not necessarily require a diagnosis of epilepsy. Generalized reflex seizures are precipitated by visual light stimulation, thinking, and decision making. These seizures usually respond to valproate treatment. Numerous triggers can induce focal reflex seizures. The triggers include reading, writing, other language functions, startle, somatosensory stimulation, proprioception, auditory stimuli, immersion in hot water, eating, and vestibular stimulation. The classification and characteristics of reflex seizures and epilepsies are described in this review. Findings on EEG and advanced neuroimaging in the reflex seizures and epilepsies, treatment and preventive options, and animal models and mechanisms are also discussed.

Animals↗

Resting and stimulated values of model parameters governing transmitter release at a synapse in Aplysia californica.

Transmitter release (R) at a synpase in Aplysia californica can be analyzed in terms of a model with the following parameters: A, the available pool of transmitter; F, the fraction of available pool released by a presynaptic action potential; M, the rate of transmitter mobilization into the available pool; D, the rate constant of demobilization of transmitter from the available pool. In the present paper we show that: (1) beginning with an analysis of the recovery from depression of the second of a pair of disolated EPSPs separated by a series of intervals of about 10-60 sec, and assuming that the recovery is due to refilling of a depleted A, it is possible to estimate resting equilibrium values of these parameters; (2) changes in these parameters when a new equilbrium state is reached after prolonged stimulation (e.g., 300 stimuli at 1/sec) can then be quantitatively determined; (3) the increased rate of transmitter release observed during and after repetitive stimulation is the consequence of increases in F and M with changes in A passively following; and (4) there are significant correlations among certain resting parameters and between the values of certain resting parameters and these parameters upon stimulation. Preparations with a large resting F tend to have a relatively small resting A. Preparations with a large resting F or M tend to increase these less with stimulation than preparations with smaller resting values of these parameters. Preparations with large stimulus-dependent increases in F tend to have large stimulus-dependent increases in M.

Animals↗

Physiological Studies on Pea Tendrils: VI. The Characteristics of Sensory Perception and Transduction.

Tendrils may be said to possess a sense of touch, and the direction and amplitude of the coiling response can be used to define the characteristics of this sense. These characteristics are, first, that the tendril will coil only in response to ventral mechanical stimulation, that this coiling can be inhibited by subsequent dorsally presented stimulation, and that dorsal stimulation alone causes no coiling. This phenomenon seems to be due to some asymmetry in the response system. Second, the nature of the response is always determined by the location (i.e., dorsal or ventral) of the last stimulation the tendril experienced. Third, the ability of dorsally presented stimulation to reverse ventrally stimulated coiling is gradually lost. Complete escape from reversibility is attained if the interval between ventral and dorsal stimulation reaches 9 minutes. Fourth, the magnitude of response is determined by both the number and the frequency of the stimuli. Both ventrally stimulated coiling and dorsally stimulated inhibition of coiling can be temporarily stopped by a 9-minute cold break at 10 C, given immediately after stimulation. As soon as the tendrils are restored to room temperature, they proceed to respond to the stimulus.The pulling ability of the tendrils generated by contact coiling, as measured by an electronic monitoring system, is of the order of 6 milligrams per minute. Whenever these two factors have been compared, pulling weight parallels contact coiling, regardless of treatment.The relationship between the stimulus and the response appears to follow rules very similar to those followed by various sensory response systems in animals. It is therefore proposed that many of these systems may have functional characteristics in common.

Journal Article↗

Subcellular localization of hydrogen peroxide production in human polymorphonuclear leukocytes stimulated with lectins, phorbol myristate acetate, and digitonin: an electron microscopic study using CeCl3.

The ultrastructural H2O2-producing site in human polymorphonuclear leukocytes (PMN) stimulated with soluble stimuli was studied using a CeCl3-technique. CeLlular aggregation and formation of small vacuoles were observed when PMN were stimulated with 100 microgram/ml concanavalin-A, 1 mg/ml phytohemagglutinin, or 100 microgram/ml wheat germ agglutinin for 10 min at 37 degrees C. Electron-dense deposits formed from the reaction of H2O2 and CeCl3 were observed on the contact surface of the plasma membrane of aggregated PMN stimulated with lectins. Treatment with 5 microgram/ml cytochalasin-B before lectin-stimulation induced an enhanced formation of vacuoles, degranuLation, rounding of the contour, cellular aggregation, and enhancement of the deposits. Phorbol myristate acetate (PMA; 100 ng/ml) induced strong leukocyte aggregation, the formation of multiple huge vacuoles, degranulation, and H2O2 production at almost all of the contact surface between adjoining PMN and between PMN and erythrocytes, mononuclear cells, or thrombocytes. In PMN stimulated with digitonin (B microgram/ml), vacuolar formation, degranulation, multiple projections on the surface, and H2O2 production on the whole surface membrane were demonstrated. It is shown that cellular aggregation and cell-to-cell contact have an important role in the induction of O2- production induced by lectins or PMA and that O2- production induced by the detergent is not dependent on leukocyte aggregation.

Cell Communication↗

Dynamic monitoring of brain activation under visual stimulation using fMRI--the advantage of real-time fMRI with sliding window GLM analysis.

An fMRI technique based on real-time analysis was applied to evaluate the advantages of dynamic monitoring of the t-statistics based on a general linear model. The temporal change of the t-statistics in V1 and V4 under four conditions of visual stimuli covering different visual fields with or without coloring was estimated using an incremental analysis and a sliding window analysis (SWA). The SWA not only visualized the dynamic change of the activation in response to the task conditions and switching, but also enabled us to evaluate the temporal correlation of the t-statistics among the four visual areas. It was suggested that the activity in the V4 was bilaterally organized, and the altering color stimuli gave stronger stimulation to the V1 than did the black and white stimuli. Although the activation map at each time point represents the brain activity during several task and rest blocks, a SWA will be useful to evaluate the transition of neuronal activation in response to several sequential task conditions. An incremental analysis will be useful to monitor the ongoing activation in real-time during the scan, since it gives a higher t-value according to the accumulation of volume data. These two methods will be complementary.

Adult↗

Effect of renal nerve stimulation on responsiveness of the rat renal vasculature.

When the renal nerves are stimulated with sinusoidal stimuli over the frequency range 0.04-0.8 Hz, low (< or =0.4 Hz)- but not high (> or =0.4 Hz)-frequency oscillations appear in renal blood flow (RBF) and are proposed to increase responsiveness of the renal vasculature to stimuli. This hypothesis was tested in anesthetized rats in which RBF responses to intrarenal injection of norepinephrine and angiotensin and to reductions in renal arterial pressure (RAP) were determined during conventional rectangular pulse and sinusoidal renal nerve stimulation. Conventional rectangular pulse renal nerve stimulation decreased RBF at 2 Hz but not at 0.2 or 1.0 Hz. Sinusoidal renal nerve stimulation elicited low-frequency oscillations (< or =0.4 Hz) in RBF only when the basal carrier signal frequency produced renal vasoconstriction, i.e., at 5 Hz but not at 1 Hz. Regardless of whether renal vasoconstriction occurred, neither conventional rectangular pulse nor sinusoidal renal nerve stimulation altered renal vasoconstrictor responses to norepinephrine and angiotensin. The RBF response to reduction in RAP was altered by both conventional rectangular pulse and sinusoidal renal nerve stimulation only when renal vasoconstriction occurred: the decrease in RBF during reduced RAP was greater. Sinusoidal renal nerve stimulation with a renal vasoconstrictor carrier frequency results in a decrease in RBF with superimposed low-frequency oscillations. However, these low-frequency RBF oscillations do not alter renal vascular responsiveness to vasoconstrictor stimuli.

Animals↗

Reactive fetal heart rate response to vibroacoustic stimulation in fetuses with low scalp blood pH.

Fetal vibroacoustic stimulation in fetuses with suspicious or ominous fetal heart rate traces in labour was followed by acid-base balance determination on fetal scalp blood within 30 min of the test. The mean fetal scalp blood pH values were significantly higher in fetuses that showed reactive responses with fetal heart rate acceleration compared with those who had no response or responded with a deceleration to the vibroacoustic stimulation (pH 7.30 and 7.22 respectively). However, acidotic scalp blood pH values (7.16 and 7.18) were found in two fetuses which had shown reactive responses both to vibroacoustic stimulation and pain stimuli with scalp blood sampling.

Acid-Base Equilibrium↗

Perception of self-motion from peripheral optokinetic stimulation suppresses visual evoked responses to central stimuli.

In a previous functional neuroimaging study we found that early visual areas deactivated when a rotating optical flow stimulus elicited the illusion of self-motion (vection) compared with when it was perceived as a moving object. Here, we investigated whether electrical cortical responses to an independent central visual probe stimulus change as a function of whether optical flow stimulation in the periphery induces the illusion of self-motion or not. Visual-evoked potentials (VEPs) were obtained in response to pattern-reversals in the central visual field in the presence of a constant peripheral large-field optokinetic stimulus that rotated around the naso-occipital axis and induced intermittent sensations of vection. As control, VEPs were also recorded during a stationary peripheral stimulus and showed no difference than those obtained during optokinetic stimulation. The VEPs during constant peripheral stimulation were then divided into two groups according to the time spans where the subjects reported object- or self-motion, respectively. The N70 VEP component showed a significant amplitude reduction when, due to the peripheral stimulus, subjects experienced self-motion compared to when the peripheral stimulus was perceived as object-motion. This finding supplements and corroborates our recent evidence from functional neuroimaging that early visual cortex deactivates when a visual flow stimulus elicits the illusion of self-motion compared with when the same sensory input is interpreted as object-motion. This dampened responsiveness might reflect a redistribution of sensorial and attentional resources when the monitoring of self-motion relies on a sustained and veridical processing of optic flow and may be compromised by other sources of visual input.

Adult↗

Impaired EMG inhibition elicited by tendon stimulation in dystonia.

OBJECTIVE: to test the effects of tendon stimulation on isometric voluntary contraction. METHODS: Twenty patients with dystonia (12 patients with generalized and eight with task-specific dystonia) and 10 normal healthy subjects participated in the study. The tendon of the extensor carpi radialis muscle was stimulated with electrical stimuli at the wrist, and the electromyogram (EMG) signal was recorded during an isometric voluntary contraction. RESULTS: In normal subjects, tendon stimulation elicited an excitatory phase (TE1), followed by a pronounced inhibitory phase (TI1) and a second excitatory phase (TE2). The three phases had similar perceptive thresholds, latencies, and durations in patients and control subjects. In patients with generalized dystonia, the TI1 area exceeded the control values (controls [mean +/- SE], 40.3 +/- 5.4; patients, 66.9 +/- 5.5; p = 0.0048, Mann-Whitney U: test). In the patients with task-specific dystonia, the TI1 area was similar to control values (controls [mean +/- SE], 40.3 +/- 5.4; patients, 54.2 +/- 4.8; p = 0.7396, Mann-Whitney U: test). CONCLUSIONS: The EMG suppression (TI1) after tendon stimulation is reduced in generalized dystonia, indicating a decreased group III-elicited presynaptic inhibition of Ia fibers. The impaired group III presynaptic inhibitory action from tendon afferents could contribute to the motor abnormalities present in dystonia. Dystonia causes widespread dysfunction of presynaptic inhibitory mechanisms in the spinal cord, involving Group I and III afferents.

Adult↗

[Functional organization of limbic brain structures during conditioned reflex activity in the dog].

In experiments on 3 dogs it was shown that instrumental defensive conditioned reflex (CR) to electrical stimulation of the hippocampus is generalized within the limbic system (LS). The rate of generalization depended on the place of testing stimuli in LS. Stimulation of the medial parts of LS at the stage of stabilized initial reflex did not produce the generalized CRs, while they appeared distinctly in response to stimulation of the lateral parts of LS. In the process of elaboration of heterogeneous CRs (defensive and alimentary) to electrical stimulation of the hippocampus, generalized conditioned reactions from some brain structures appeared in both situations to the same degree while from other structures--with considerable differences. These data point to a possible participation in the genesis of the generalized CRs both of signal and reinforcing brain mechanisms.

Amygdala↗

Limbic epileptogenicity, cell loss and axonal reorganization induced by audiogenic and amygdala kindling in wistar audiogenic rats (WAR strain).

Audiogenic seizures are a model of generalized tonic-clonic brainstem-generated seizures. Repeated induction of audiogenic seizures, in audiogenic kindling (AuK) protocols, generates limbic epileptogenic activity. The present work evaluated associations between permanence of AuK-induced limbic epileptogenicity and changes in cell number/gluzinergic terminal reorganization in limbic structures in Wistar audiogenic rats (WARs). Additionally, we evaluated histological changes after only amygdala kindling (AmK) and only AuK, and longevity of permanence of AuK-induced limbic epileptogenicity, up to 160 days. WARs and Wistar non-susceptible rats were submitted to AuK (80 stimuli) followed by both 50 days without acoustic stimulation and AmK (16 stimuli), only AmK and only AuK. Cell counting and gluzinergic terminal reorganization were assessed, respectively, by using Nissl and neo-Timm histochemistries, 24 h after the last AmK stimulus. Evaluation of behavioral response to a single acoustic stimulus after AuK and up to 160 days without acoustic stimulation was done in another group. AuK-induced limbic epileptogenicity developed in parallel with a decrease in brainstem-type seizure severity during AuK. AmK was facilitated after AuK. Permanence of AuK-induced limbic epileptogenicity was associated with cell loss only in the rostral lateral nucleus of amygdala. Roughly 20 generalized limbic seizures induced by AuK were neither associated with hippocampal cell loss nor mossy fiber sprouting (MFS). AmK developed with cell loss in hippocampal and amygdala nuclei but not MFS. Main changes of gluzinergic terminals after kindling protocols were observed in amygdala, perirhinal and piriform cortices. AuK and AuK-AmK induced a similar number and type of seizures, higher than in AmK. AmK and AuK-AmK were associated with broader cell loss than AuK. Data indicate that permanent AuK-induced limbic epileptogenicity is mainly associated to gluzinergic terminal reorganization in amygdala but not in the hippocampus and with no hippocampal cell loss. Few AmK-induced seizures are associated to broader and higher cell loss than a higher number of AuK-induced seizures.

Acoustic Stimulation↗

Responses of human single motor units to transcranial magnetic stimulation.

Transcranial electromagnetic brain stimuli elicit a complex response in the electromyogram of active human hand muscles. Relatively weak stimuli evoke a short-latency primary response via a presumably monosynaptic corticospinal path. This is followed by a silent period that is terminated by a second peak at a latency of 50-80 ms. The responses evoked in single motor units in flexor digitorum profundus (FDP) were recorded. Responses were elicited at the second-peak latency only in trials in which no primary response was elicited in that unit, and only when the stimulus was given during the first half of the interspike interval (ISI). When given during the second half of the ISI, the same stimulus evoked a primary response but no second peak response. Stronger stimuli suppressed the second peak by evoking a primary response in more trials. Having discharged at about 20 ms latency, the parent motoneurone was unable to discharge again at second-peak latency, 30-60 ms later. The response at second-peak latency was not modified by disengaging both FDP and the extensors of the distal interphalangeal joint. Hence, this response is not secondary to a stretch reflex provoked by activation of the finger extensors, nor is it the result of a cutaneous signal resulting from movement of the finger. The latencies suggest that the corticospinal volley evokes a beta-motoneurone-mediated twitch in FDP muscle spindles, which elicits an afferent volley that activates the motoneurone reflexly. The first 100 ms or so of the silent period is due to the realignment of the first post-stimulus spike in most trials to corticospinal latency; i.e. this is not necessarily the result of an inhibitory or disfacilitatory process. Still stronger stimuli increase the duration of the ISI in which the stimulus is given, indicating the presence of an inhibitory/disfacilitatory process.

Adult↗

Ion specificity of rat chorda tympani fibers to chemical and electrical tongue stimulations.

Responses of rat single chorda tympani fibers to ionic chemical stimuli and anodal tongue stimulations with ionic bathing solutions were examined. Fourteen out of 30 fibers showed the highest sensitivities to NaCl for both chemical and electrical stimulations, whereas the remaining 16 fibers showed almost no ion specificity for electrical stimulation even though most of them have the highest sensitivities to HCl for chemical stimulation. Ion specificity for electrical stimulation was significantly smaller than that for chemical stimulation.

Animals↗

Motor unit excitability changes mediating vestibulocollic reflexes in the sternocleidomastoid muscle.

OBJECTIVE: To investigate the patterns of motor unit firing in single motor units from the sternocleidomastoid (SCM) muscles in response to stimuli previously shown to be capable of evoking vestibulocollic reflexes (loud clicks and electrical stimulation) and to relate these to the previously described surface potentials (VEMPs, vestibular evoked myogenic potentials) evoked by the same stimuli. METHODS: Eleven male subjects (30-43-years-old) were studied. Local anaesthetic was used to block the SCM and confirm that the surface potentials (p13n23) arose from it. At another time, fine wire or needle electrodes were used to record single motor unit activity and peristimulus time histograms were constructed. RESULTS: Local anaesthetic block reduced or abolished the p13n23 response in 5 of 6 subjects. A total of 94 histograms of motor unit discharges were recorded. The excitability changes seen were always small. Loud click stimuli given ipsilaterally evoked short latency (mean 14.2 ms, uncorrected for triggering delays), and short duration (mean 3.6 ms) inhibition. Contralaterally, the effect was excitatory (latency 11.9 ms, uncorrected, mean duration 2.3 ms). For electrical stimulation, short latency inhibition occurred ipsilateral to the cathode (average latency 14.0 ms, uncorrected, mean duration 2.9 ms) and excitation occurred contralaterally. CONCLUSIONS: We confirmed that the SCM is the sole or dominant source of the VEMPs recorded from electrodes over it. Short latency, short duration motor unit firing changes are evoked in SCM by loud clicks and electrical stimulation, stimuli known to be capable of evoking vestibulocollic reflexes. VEMPs beginning with a positivity correspond to inhibition of the underlying motor unit firing and those starting with a negativity correspond to an underlying excitation, findings consistent with intracellular recordings of otolith effects. Qualitative explanations of how the surface potentials are generated by these excitability changes and relating to other properties of the surface responses are proposed. SIGNIFICANCE: This study has shown consistent patterns of single motor unit firing which underlie VEMPs evoked by both clicks and short duration galvanic stimulation.

Acoustic Stimulation↗