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Responses of single neurons in the parietoinsular vestibular cortex of primates.

1. Neurons activated by stimulation of the horizontal and/or vertical vestibular semicircular canals were recorded in the parietoinsular vestibular cortex in four awake Java monkeys (Macaca fascicularis) and three squirrel monkeys (Saimiri sciureus). Steady tilt in darkness or during illumination of a vertically striped cylinder or of the normal laboratory surroundings did not lead to a significant change in PIVC neuron activity. Thus vestibular input to this cortical region seems to be restricted to signals originating in the semicircular canal receptors. 2. Vestibular stimulation in the three main experimental planes (roll, yaw, and pitch) and in planes in between provided clear evidence that optimum activation can be found in planes that do not coincide with the planes of the semicircular canals but are distributed over all possible spatial planes through the head. 3. Definite evidence of clustering in subdivisions of PIVC of neurons responding to the same optimum rotation plane was obtained in squirrel monkeys and is also suggested to exist in PIVC of Java monkeys. 4. Nearly all neurons responding to vestibular stimulation were also activated by visual large-field movement (optokinetic stimulation). Responses to optokinetic stimuli were always at optimum when the direction of the movement pattern corresponded to the optimum vestibular plane. Two classes of visual-vestibular interaction were found: Synergistic neurons were those PIVC cells with the strongest response to visual movement stimulation in the opposite direction to that leading to a maximum response to vestibular stimulation. Antagonistic neurons had a response maximum when the visual stimulus was moved in the direction of optimum vestibular stimulation. 5. Most PIVC neurons responded to stimulation of the deep mechanoreceptors in the neck region. This input from the neck receptors was tested quantitatively only in the horizontal plane (trunk rotation with the head fixed in space or head rotation with the trunk fixed in space). It interacted with vestibular signals at the PIVC neurons either in an antagonistic or a synergistic manner, the latter meaning activation during rotation of the head in the same direction as that leading to activation induced by semicircular canal stimulation. 6. In addition to the direction-specific vestibular, visual, and neck receptor inputs, a rather complex somatosensory input to PIVC neurons exists, including responses to stimulation of mechanoreceptors of the skin, the muscles, and the joint receptors of legs and arms. Total body vibration also led to activation of some of the neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Electrical stimulation of the dorsal hippocampus caused a long lasting inhibition of ACTH and adrenocortical responses to photic stimuli in freely moving rats.

The effect of a single train of electrical hippocampal stimulation on ACTH and corticosterone (CS) responses to subsequent photic stimulation was studied in freely moving male rats. The hippocampal stimulation inhibited the stress-induced rise [corrected] in serum CS levels up to 150 h when compared to sham stimulated animals. This effect did not exist at 300 h following stimulation. This sustained hippocampal inhibitory effect on the adrenocortical response, which was not reported previously, was partially abolished by section of the dorsal fornix. The present data demonstrate that dorsal hippocampal stimulation has a long lasting inhibitory effect on pituitary adrenocortical secretion following neural stimuli and this is partially mediated by the dorsal fornix.

Adrenal Cortex↗

Specific role for the extracellular signal-regulated kinase pathway in angiotensin II- but not phenylephrine-induced cardiac hypertrophy in vitro.

The study addressed the question of why in adult ventricular rat cardiomyocytes ERK activation is required for the hypertrophic stimulation caused by angiotensin II but not in the case of alpha-adrenoceptor stimulation. We therefore compared in the same culture system the intracellular signaling steps that are involved in inducing the hypertrophic growth evoked by stimulating either of these two receptors. alpha-Adrenoceptor stimulation strongly increased protein synthesis ([14C]phenylalanine incorporation) up to 53% in a PKC- and p70s6k-dependent, but ERK-independent way. In contrast, angiotensin II increased protein synthesis less efficiently (by 23%), in a PKC-, p70s6k-, but ERK-dependent way. The kinetics of activation for ERK were different for the two hypertrophic stimuli: alpha-adrenoceptor stimulation caused a rapid and transient activation, but angiotensin II caused a rapid and sustained activation. In contrast to alpha-adrenoceptor stimulation, angiotensin II activated calcium-independent PKC isoforms but not calcium-dependent PKC isoforms. In conclusion, ERK activation by angiotensin II is sustained and leads to an increase in protein synthesis on adult ventricular cardiomyocytes, but ERK activation by alpha-adrenoceptor stimulation is transient and not involved in hypertrophic growth responsiveness. The ERK-dependent pathway seems to be less efficient than ERK-independent pathways. The difference in the hypertrophic responsiveness of cardiomyocytes exposed to either of the two stimuli may be explained by the activation of different PKC isoform types.

Angiotensin II↗

[Correlation of stimulus-induced ventricular echo beats and left ventricular function in patients without ventricular tachycardia].

110 patients (105 male, 5 female, mean age +/- S.D.: 52.9 +/- 5.9 years) with and without coronary artery disease were prospectively studied by programmed right ventricular stimulation (single and double premature stimuli during sinus rhythm and a paced ventricular drive of rates of 120, 140, 160 and 180 b.p.m.). The incidence of ventricular echobeats (VE) was correlated with angiographic and electrocardiographic findings. The end of the stimulation protocol was reached as soon as four or more ventricular echobeats were initiated. 0 to 3 VE occurred in 61/110 patients, 4-9 VE in 31 patients (28%), and greater than or equal to 10 VE were induced in 16 patients. Four or more VE were initiated in 68% of cases up to a paced ventricular rhythm of 120 b.p.m. after one or two premature stimuli. Patients with abnormal results of stimulation showed a tendency to an increase in the frequency of ventricular extrasystoles and couplets during long-term ECG recording. 86% of the patients with normal angiographic findings had 0-3 VE and 14% greater than or equal to 4 VE. In 49% of the patients with abnormal left ventricular function, 0-3 VE and in 51%, greater than or equal to 4 VE could be induced. The type of left ventricular contraction abnormality was significantly correlated to the results of programmed ventricular stimulation. greater than or equal to 4 VE were observed in 74% of patients with anterior wall myocardial infarction. Patients with inferior wall myocardial infarction had greater than or equal to 4 VE in 54% of cases. Ventricular tachycardia was induced in 30% of patients with anterior and in only 12% of patients with inferior wall myocardial infarction (n.s.). To conclude, this prospective study has shown a correlation between the incidence of inducible ventricular echobeats in response to programmed ventricular stimulation and left ventricular function. The prognostic significance of these findings has to be assessed.

Electric Stimulation↗

Cardiac electrical responses to vagal stimulation of fibers to discrete cardiac regions.

We stimulated regional intracardiac parasympathetic nerve fibers to the atrioventricular (AV) nodal area (AVP stimuli) or to the sinoatrial (SA) nodal area (SAP stimuli) in autonomically decentralized, anesthetized dogs. AVP stimuli increased the AV interval (AV conduction time); the magnitude of the response depended directly on the stimulation frequency. AVP stimuli did not alter the atrial interval (heart period) in spontaneously beating hearts. The magnitude of the negative dromotropic response increased when the atrial interval was shortened. SAP stimuli increased the atrial interval, and the magnitude of the response depended directly on the stimulation frequency. SAP stimuli evoked little or no change in the AV interval in the unpaced heart. When the atrium was paced, SAP stimuli did not change the AV interval in about half of the preparations, and there was a small but significant change in the remaining preparations. The negative dromotropic or chronotropic response to AVP or SAP stimuli was potentiated by physostigmine and blocked by atropine. These results suggest that 1) AVP stimuli induce a selective negative dromotropic response, and 2) this negative dromotropic effect is secondarily affected by heart period, by the pacemaking site, and by atrial activation patterns, but it does not affect the sinus cycle length in the dog heart.

Animals↗

Role of intradental A- and C-type nerve fibres in dental pain mechanisms.

The arousal of the two components of pain (the first rapid or sharp pain and the second dull pain) are considered to be related to activation of A delta- and C-type nociceptive primary afferents, respectively. The same dichotomy of pain sensations may also exist in teeth, although due to the short distance between the site of stimulation and the brain the two sensations might not be as clearly separated as in stimulation of, for example, the extremities. The sensations evoked by stimulation of human teeth vary according to the type of the stimuli applied. Low-intensity electrical stimulation is able to induce non-painful (prepain) sensations. At high current intensities pain is evoked. Drilling, probing and air-drying of exposed dentin induce only pain. Most studies also indicate that thermal stimulation only induces painful sensations. The quality of dental pain can vary. Typically, dentinal stimulation of teeth with healthy pulps induces sharp pain. On the other hand intense heat stimulation can result in dull pain which radiates to a wider area of the face and jaws. This component of the stimulus-induced pain seems to share some characteristics of toothache associated with painful pulpitis. Single fibre recordings of intradental nerve activity in experimental animals have shown that in addition to A-fibres a considerable number of C-type primary afferents innervate the dental pulp. This is in accordance with the results of neuroanatomical studies, which indicate that 70-80% of pulpal axons in human, monkey, dog, and cat teeth are unmyelinated. Intradental A- and C-fibre groups seem to be functionally different and can be activated separately by certain external stimuli. Comparison of the response characteristics of the pulp nerve fibres and the sensations induced from human teeth indicate that: 1) A-fibres are responsible for the sensitivity of dentine and thus for the mediation of the sharp pain induced by dentinal stimulation, 2) Prepain sensations induced by electrical stimulation result from activation of the lowest threshold A-fibres some of which can be classified as A beta-fibres according to their conduction velocities. Comparison of the responses of the A beta- and A delta-fibres indicate that they belong to the same functional group, 3) Intradental C-fibres are activated only if the external stimuli reach the pulp proper. Their activation may contribute to the dull pain induced by intense thermal stimulation of the tooth and to that associated with pulpal inflammation.

Animals↗

Intracellular studies of the convergence of sensory input on caudate neurons of cat.

Quantitative analyses of the intracellular responses to peripheral stimuli were made in a 172 neurons recorded in the head of the caudate nucleus (Cd) of cat. Responsiveness of Cd neurons was tested using auditory and somatosensory stimuli which were presented unilaterally. We found that most cells (99%) responded to both auditory and somatosensory stimuli. Excitation followed by inhibition (i.e. E-I response) was the primary pattern of intracellular response occurring approximately 75% of the time. Qualitative and quantitative analyses revealed marked similarities in the amplitudes and time courses of the intracellular responses following supramaximal stimulation of the peripheral stimuli studied. Similarly, analyses of 40 pairs of simultaneously recorded neurons revealed a marked homogeneity in the intracellular responses to the same stimulus even though the recordings were made several mm apart. The most striking feature of the simultaneous recordings was that the peaks of the initial E-I response and the afterpotentials often occurred in register after a peripheral stimulus. Furthermore, changes in the responses of pairs of simultaneously recorded neurons co-varied. Because the striatum typically demonstrates spontaneous rhythmic activity, these data suggest that a peripheral stimulus has the potential of briefly synchronizing Cd's neuronal activity.

Animals↗

The effect of social isolation on androgen and corticosteroid levels in a cichlid fish (Haplochromis burtoni) and in swordtails (Xiphophorus helleri).

The blood androgen and glucocorticoid levels of male Haplochromis burtoni and Xiphophorus helleri were measured in socially isolated individuals (8 and 4 weeks, respectively) and nonisolated controls. In both species social isolation leads to significant reductions of mean concentrations and variances, both for androgens and corticosteroids. It is known for H. burtoni--and new evidence for X. helleri is presented--that social isolation reduces aggressivity in nonescalating situations. It is proposed that social stimuli in both species stimulate the testes to produce more androgenic hormones, and that this can lead to higher levels of aggression. At least in tropical fish species the androgenic optimum for defending a territory or a social status may be much more controlled by social stimuli than previously realized.

Adrenal Cortex Hormones↗

Multiple pathways for signal transduction in the regulation of arachidonic acid metabolism in rat peritoneal macrophages.

The roles of guanine nucleotide-binding proteins (G-proteins) and cyclic AMP (cAMP) in signal-transduction of inflammatory stimuli leading to arachidonic acid metabolism in resident rat peritoneal macrophages (RPM) were investigated. Opsonized zymosan, targeting multiple receptors and latex particles coated with IgG (latex-IgG), targeting Fc receptors, were used as models of in vivo inflammatory stimuli encountered by macrophages. A comparison of the patterns of eicosanoid products produced in response to these stimuli showed differences: opsonized zymosan stimulated production of more leukotriene B4 (LTB4) than prostaglandin E2 (PGE2), while latex-IgG stimulated production of more PGE2 than LTB4. Non-selective stimulation of G-proteins by GTP and non-hydrolyzable analogs of GTP also stimulated arachidonic acid metabolism; these agents were not selective for PGE2 or LTB4 production. Cholera toxin, however, selectively stimulated production of PGE2 rather than LTB4 and also increased intracellular cAMP concentrations. The increased cAMP did not appear to mediate cholera toxin stimulation since forskolin, which also increased cAMP, was inhibitory to PGE2 production. This suggests that latex-IgG and cholera toxin may activate arachidonic acid metabolism through a G-protein other than Gs to induce PGE2 production specifically. The effects of pertussis toxin were biphasic: a partial inhibitory effect was observed at a low concentration of pertussis toxin (1 ng/ml) on opsonized zymosan or latrix-IgG stimulated arachidonic acid metabolism, while a high concentration of pertussis toxin (100 ng/ml) augmented the stimuli. A pertussis toxin-sensitive G-protein, possibly Gi, may therefore mediate a portion of the stimulatory signals. We have concluded that multiple pathways probably exist for opsonized zymosan and latex-IgG stimulation of arachidonic acid metabolism potentially involving multiple G-proteins.

Animals↗

Visual resolution with epi-retinal electrical stimulation estimated from activation profiles in cat visual cortex.

Blinds with receptor degeneration can perceive localized phosphenes in response to focal electrical epi-retinal stimuli. To avoid extensive basic stimulation tests in human patients, we developed techniques for estimating visual spatial resolution in anesthetized cats. Electrical epi-retinal and visual stimulation was combined with multiple-site retinal and cortical microelectrode recordings of local field potentials (LFPs) from visual areas 17 and 18. Classical visual receptive fields were characterized for retinal and cortical recording sites using multifocal visual stimulation combined with stimulus-response cross-correlation. We estimated visual spatial resolution from the size of the cortical activation profiles in response to single focal stimuli. For comparison, we determined activation profiles in response to visual stimuli at the same retinal location. Activation profiles were single peaked or multipeaked. In multipeaked profiles, the peak locations coincided with discontinuities in cortical retinotopy. Location and width of cortical activation profiles were distinct for retinal stimulation sites. On average, the activation profiles had a size of 1.28 +/- 0.03 mm cortex. Projected to visual space this corresponds to a spatial resolution of 1.49 deg +/- 0.04 deg visual angle. Best resolutions were 0.5 deg at low and medium stimulation currents corresponding to a visus of 1/30. Higher stimulation currents caused lower spatial, but higher temporal resolution (up to 70 stimuli/s). In analogy to the receptive-field concept in visual space, we defined and characterized electrical receptive fields. As our estimates of visual resolutions are conservative, we assume that a visual prosthesis will induce phosphenes at least at this resolution. This would enable visuomotor coordinations and object recognition in many indoor and outdoor situations of daily life.

Animals↗

Homotopy and heterotopy and the bilateral field advantage in the Dimond paradigm.

Pairs of homotopic and heterotopic visual bilateral stimuli and pairs of unilateral visual stimuli were presented to 12 normal right-handed university students requiring a key press if they were of the same form. As predicted from the known histology of the corpus callosum (massive preponderance of homotopic fibers), homotopic presentations yielded significantly faster reaction times than heterotopic stimulations. Bilateral pairs of stimuli were also advantaged in comparison with unilateral trials, replicating Sereno and Kosslyn [Sereno, A. B., & Kosslyn, S. M. (1991). Discrimination within and between hemifields: a new constraint on theories of attention. Neuropsychologia, 29, 659-675]. Moreover, certain attentional processes have never been investigated in the Dimond paradigm and this study provides evidence to the effect that discriminative reaction times to stimulus pairs are strongly influenced by their proximity to the fixation point. In similar previous experiments, the homotopy/heterotopy observation and the bilateral field advantage may have been distorted by that particular confound, as well as several others.

Adult↗

Reflex vagal inhibition of gastric motility by intestinal nociceptive stimulation in the cat.

The effect on gastric motility of various irritative stimuli to the small and large intestine and peritoneum were studied in anesthetized cats. Mechanical stimulation of the jejunum or colon elicited gastric relaxation, which was not blocked by antiadrenergic or anticholinergic drugs but was abolished by vagotomy. Long-lasting gastric relaxation with similar characteristics was observed on jejunal surgery, spontaneous peritonitis, or chemical irritation of the abdominal cavity with acid or methanol. Diathermic lesions of the gut caused less gastric inhibition than mechanical and chemical stimuli. Afferent electric stimulation of jejunal and colonic nerves induced gastric relaxation with similar characteristics as mechanical stimulation in the same regions. It is concluded that mechanical and chemical irritation of the gut and intestinal surgery and peritonitis are accompanied by a gastric relaxation due to activation of the vagal nonadrenergic inhibitory fibers to the stomach. This vagal mechanism is suggested to be important for the suppression of gastric motility in paralytic ileus.

Animals↗

Activation of the metabolism of the fatty acyl group in granulocyte phospholipids by phorbol myristate acetate.

Phorbol myristate acetate is known to reproduce the stimulated oxidative activities characteristic of phagocytosis and its initial action is on the cell membrane. In the present study the effect of phorbol myristate acetate on the metabolism of the fatty acyl groups of granulocyte phospholipids was examined and compared with that of phagocytic stimuli. Phorbol myristate acetate stimulated the labeling of phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol by [1-14C]palmitic acid but not by [U-14C]glycerol, whereas starch granules selectively increased the labeling of phosphatidylinositol by both radioactive tracers. Labeled palmitic acid was found at both sn-1- and sn-2-positions of phospholipids and more radioactivity was recovered from the 2-position. The radioactivity at both positions was enhanced in stimulated cells. These data suggest that phorbol myristate acetate increased palmitic acid incorporation into glycerophospholipids by increasing the acylation of the lyso derivatives and that starch granules enhanced the formation of phosphatidylinositol via de novo synthesis and acylation of the lyso derivative as well. Both phorbol myristate acetate and starch granules selectively augmented the incorporation of [1-14C]arachidonic acid into phosphatidylinositol which exhibited the highest specific radioactivity among the phospholipids in control and in stimulated cells. The possible significance of the increased incorporation of arachidonic acid into phosphatidylinositol is discussed.

Animals↗

[Comparative evaluation of the results of Holter monitoring and programmed ventricular stimulation in patients with ischemic heart disease].

24-hour ECG Holter monitoring and programmed ventricular stimulation were performed in 81 patients (64 males and 17 females aged 35-65). No ++anti-arrhythythmic agents nor beta-blockers were administrated. 58 patients suffered from myocardial infarction in the past, and 38 had a history of ventricular tachycardia. Right atrial and ventricular stimulation (in 7 patients also left ventricular stimulation) was performed using stimuli of a 2 ms pulse width. 24-hour ECG Holter monitoring was recorded on a magnetic tape from two bipolar precordial leads. Both examinations results were compared to assess correlation between ECG Holter monitoring parameters and inducibility of VT or VF by programmed stimulation. Significant correlation was stated among occurrence of: 1) spontaneous sustained ventricular tachycardia and induced by stimulation monomorphic sustained VT (p less than 0.005) as well as estimated both sustained and nonsustained VT (p less than 0.010) 2) spontaneous nonsustained VT and induced by stimulation sustained or nonsustained monomorphic VT (p less than 0.025). There was no correlation between spontaneous ventricular arrhythmias estimated by Lown and Wolf's classification and possibility to induce monomorphic VT as well as between any of ECG Holter monitoring parameters and polymorphic VT or ventricular fibrillation induced by stimulation. Aggressiveness extent of stimulation protocol necessary to induce monomorphic VT was similar in patients with or without VT recorded by Holter method.

Adult↗

Neglect as a deficit determined by an imbalance between multiple spatial representations.

A previous study on neglect suggested that at least two hand parameters are crucial in producing an amelioration of neglect: the hand (left or right) and the spatial position of the hand (left or right). The improvement observed in perceiving left targets when the left hand acts in the left space can be due either to proprioceptive or to visual cuing. The stimulated left hand located in the left space may act as a powerful visual cue for the enhancement of the left visuo-spatial representation, in the same way as any other visual stimulus presented in the periphery of the visual field. Alternatively, it may be that the perceived hand location (due to the activation of the proprioceptive system) acts as an attentional field able to enhance the representation of the left space. In order to disentangle these two hypotheses, in the present study a naming task was executed by a group of neglect patients and by a control group. The subjects had to name all the objects depicted on a sheet of paper which were reflected on a mirror that inverted right and left space. While doing the naming performance, the subjects passively moved either the right or the left hand, in the left or right space. Stimuli and hand were reflected in the mirror that inverted right and left space and direct view of the stimuli and of the stimulated hand was prevented by a board. The results show that patients were more accurate at naming stimuli reflected in the left side of the mirror when the left hand was located and moved on the left side. In this condition, however, the left hand was seen in the right side of the mirror. It is therefore clear that the better performance was not due to visuo-spatial cuing but to a proprioceptive cuing effect. The results are discussed in terms of the relevance of personal and peripersonal spatial activation in the modulation of extrapersonal visual neglect. The coactivation of different spatial representations seems to be very influential on stimulus coding, thus confirming that spatial awareness is strictly related to the joint activity of multiple brain maps.

Aged↗

[Examination of the visual system with transcranial magnetic stimulation].

The influence of transcranially applied magnetic stimuli on the function of the afferent (sensory) and efferent (motor) parts of the visual system have been discussed. Excitatory (positive) phenomena are subjective photic sensations (phosphenes) which can be elicited by transcranial magnetic stimulation over occipital parts of the skull. The phosphenes appear on the left or right side of the visual field depending upon the direction of the coil currents, which determines whether the visual cortex of the right or the left hemisphere is activated. The configuration of the phosphene fields hints at an excitation of the primary visual cortex (Brodmann's area 17). However, magnetic brain stimulation also produces inhibitory (negative) phenomena. When strong magnetic field pulses are applied over the primary visual cortex, foveally presented visual stimuli cannot be identified even when no phosphenes are perceived at the same time. Depending on the position of the stimulation coil, this suppression of perception can be restricted to visual stimuli presented on the right, or left of, above or below the fixation point. No generation or disturbance of eye movements by transcranial magnetic stimulation has been reported before, except for a delay of saccades within a reaction time paradigm.

Animals↗

Lesion site in idiopathic bilateral vestibulopathy: a galvanic vestibular-evoked myogenic potential study.

CONCLUSION: The result suggests that patients with idiopathic bilateral vestibulopathy may have nerve lesions when the inferior nerve system is affected, while the inferior vestibular nerve system may be spared. OBJECTIVE: To clarify the lesion site in idiopathic bilateral vestibulopathy, an acquired bilateral vestibulopathy of unknown cause. MATERIAL AND METHODS: Two 75-year-old males diagnosed with idiopathic bilateral vestibulopathy were enrolled. Both showed absent or highly decreased responses on the caloric test on both sides. They underwent vestibular-evoked myogenic potential (VEMP) testing by means of acoustical and electrical stimulation. As acoustic stimulation, 95 dB nHL clicks and short tone bursts (500 Hz) were presented, while 3 mA (1 ms) short-duration galvanic stimuli were presented as electrical stimulation. Responses were recorded on the sternocleidomastoid muscles. RESULTS: Both patients showed unilateral absence of VEMPs with both acoustic and short-duration galvanic stimuli.

Acoustic Stimulation↗

Supramaximal stimuli do not evoke a maximal contraction in urinary bladder smooth muscle fibers.

BACKGROUND: Smooth muscle fibers can be stimulated with an electrical field, high potassium or carbachol. We studied the effect of combined, supramaximal stimulation on the isometric force and the maximum shortening velocity of the pig urinary bladder. MATERIALS AND METHODS: After determining the dose response curve of each stimulation type, we stimulated 8 fibers with cumulative addition of supramaximal stimuli. RESULTS: The isometric force elicited with either potassium, carbachol or electrical field stimulation alone was the same for each stimulus. After addition of a second or third different supramaximal stimulus, the force further increased to a value that was on average 40% higher. CONCLUSIONS: Carbachol, high potassium or electrical field stimulation work through different stimulation pathways. Maximum stimulation with one of the stimuli does not result in a maximum isometric force development and maximum shortening velocity.

Animals↗