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Importance of attentional mechanisms in audiovisual links.

The effect of auditory cues at different levels of visual processing was examined by using a visual "conjunction of features" discrimination task (experiment 1) and a "feature" discrimination task (experiment 2). In both experiments the visual target, appearing either on the left or the right of Ss' midline, was preceded by a brief tone either spatially proximal or distal to the target. In the "conjunction" task, subjects had to discriminate the orientation of a T flanked with T distractors of different orientations. In this task, assumed to require focused attention, discrimination accuracy was increased when the sound cue occurred at the subsequent visual target location and was decreased when it occurred at its alternative location. In the "feature" experiment, subjects had to discriminate the orientation of a line segment (+/-45 degrees) presented among line segment distractors. Accuracy was not affected, either when the sound was proximal or when it was distal to the location of the visual target. Results suggest that the early processing of sensory information is modality specific and that interference of auditory stimulation with visual stimuli is more pronounced as the processing of visual stimuli requires focused attention.

Acoustic Stimulation↗

[Somatosensory evoked potentials following tactile skin stimulation].

Somatosensory evoked potentials were recorded for tactile stimuli applied to the fingers II and V as well as paravertebrally. The advantage of the painless mechanical stimuli is their specificity and the well defined stimulus localization. The question was therefore if the evoked responses are clearly demarcated. Nack potentials (N22: 22.5 and 22.3 ms) as well as cortical SEP's (P1: 33.2 and 32.8 ms) were easily to derive. It was also possible to get SEP's for segmental paravertebral tactile stimuli. For the finger stimulation an Erb's potential could not be recorded reliably.

Adolescent↗

CpG oligodeoxynucleotides overcome the unresponsiveness of neonatal B cells to stimulation with the thymus-independent stimuli anti-IgM and TNP-Ficoll.

Neonates are very vulnerable to pathogenic encapsulated bacteria due to their inability to mount an antibody response to capsular polysaccharides, which are thymus-independent type 2 (TI-2) antigens (Ag). Oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotides induced neonatal B cells to proliferate to anti-IgM, a TI-2 stimulus. CpG ODN inhibited the spontaneous and B cell receptor-mediated apoptosis of neonatal B cells and reduced the amount of the pro-apoptotic Bcl-xS, strongly correlated with anti-IgM-induced apoptosis of neonatal B cells. CpG ODN protected neonatal B cells from apoptosis by down-regulation of the Bcl-xS protein. Neonatal B cells underwent polyclonal differentiation upon stimulation with CpG ODN, but unlike in adult B cells, this was not preceded by IL-6 secretion. CpG ODN stimulated neonatal B cells to mount an Ag-specific antibody response to TNP-Ficoll, another TI-2 Ag. Thus CpG ODN could provide a novel approach to induce the immune system in neonates to respond to harmful encapsulated bacteria.

Animals↗

[Physiological evaluation of vestibular training load].

Objective. To evaluate the effects of vestibular training by observing the variations of the physiological indices. It is helpful in grasping the training load, setting down and implementing the training plan. Method. 10 healthy subjects received linear acceleration, continuous Coriolis acceleration and discontinuous Coriolis acceleration stimuli on different dates. The stimulus was stopped when there were slight autonomic nervous symptoms, ECG, EGG and BP were recorded before during and after the stimuli. Computerized Dynamic Posturography (correction of Postrograph) (CDP) was tested before and after experiment. Result. One subject finished the training of the three stimuli with only slight autonomic nervous symptoms. The CDP tests pre- and post-experiment indicated that for most subjects the contribution of vestibular function in maintaining dynamic posture equilibrium increased after the linear acceleration stimuli, but decreased after continuous Coriolis acceleration stimuli, and there was great individual difference after discontinuous Coriolis acceleration stimuli because the stimulation was relatively heavy. The equilibrium score in SOT2 decreased significantly after linear acceleration stimuli, and increased significantly after discontinuous Coriolis acceleration stimuli. Conclusion. The training methods we designed and used in this experiment are feasible, and the required training load can be reached. EGG, BP and the percentage of LF (low frequency) in ECG R-R power spectrum can reflect the subject's condition when the period stimuli stopped. It provided important reference in the determination of training stimulation load.

Acceleration↗

Mechanism of stimulation of aortic chemoreceptors by natural stimuli and chemical substances.

1. Impulses were recorded in single fibres of aortic chemoreceptors of cats anaesthetized with chloralose. There was no demonstrable difference between the responses of the endings of medullated and non-medullated fibres respectively to any of the natural stimuli, such as hypoxia, reduction in blood pressure, or reduction in O(2) content. This indicates that the generator processes are qualitatively and quantitatively identical at the endings of both types of fibres.2. Most of the endings were practically silent while ventilating the lungs with air. The maximum frequency of discharge averaged over 4-10 sec while ventilating the lungs with 4% O(2) ranged from 1.5 to 24 impulses/sec; in most fibres (twenty-one out of twenty-six endings) it was less than 12 impulses/sec.3. All the chemoreceptors tested were considerably stimulated following administration of 0.2 or 2% CO at a time when the O(2) content was greater than 4 ml./100 ml.4. All the chemoreceptors were markedly and rapidly stimulated following circulatory arrest while the cat was ventilated with air. This stimulation fell considerably within 3 min of circulatory arrest. Very little or no excitation followed circulatory arrest while ventilating the cat with pure N(2). These results suggest that excitation following circulatory arrest is not produced by a metabolite.5. There was a remarkable difference between the sensitivities of endings of medullated and non-medullated fibres to drugs. The former were either unaffected by relatively large doses of ACh (100-200 mug) or phenyl diguanide, or if they were stimulated, the excitation so produced was much less than that produced in endings of non-medullated fibres. This supports the hypothesis that drugs produce their effects by an action at the regenerative regions of the endings, i.e. regions where the nerve impulse is initiated (Paintal, 1964). It also indicates that ACh is not likely to be a transmitter in the normal processes of excitation of chemoreceptors.6. A mechanism of stimulation of chemoreceptors not involving metabolites is presented.

Journal Article↗

Neuronal responses of the rat amygdala during extinction and reassociation learning in elementary and configural associative tasks.

To investigate functional heterogeneity within the amygdala in appetitive conditioned instrumental behaviours, neuronal activity was recorded from the amygdala of behaving rats during learning and discrimination of conditioned sensory stimuli associated with or without reinforcement [sucrose solution, intracranial self-stimulation (ICSS)]. Sensory stimuli included auditory (tone), visual (light) and configural (simultaneous presentation of tone and light) stimuli. The rat was trained to lick a spout protruded close to its mouth just after a conditioned sensory stimulus to obtain a reward. Of the 609 neurons recorded from the amygdala and amygdalostriatal transition area, 154 responded to one or more sensory stimuli. The 62 amygdalar neurons responded strongly to certain conditioned sensory stimuli associated with rewards. Of these 62 neurons, 45 were tested with the extinction trials. Responses of 31 neurons to conditioned stimuli were finally extinguished, and those of the remaining 14 were not extinguished. Furthermore, responses of 26 of these 31 neurons resumed in the relearning trials (plastic neurons), suggesting that these sensory responses were associative rather than just responses to physical properties of the stimuli. These plastic neurons were located mainly in the basolateral nucleus of the amygdala, and responses of the plastic neurons were correlated with behavioural responses. These results suggest that the basolateral nucleus is crucial in associative learning between sensory information and affective significance for behavioural outputs in appetitive conditioned instrumental behaviours.

Acoustic Stimulation↗

Topography of somatosensory processing: cerebral lateralization and focused attention.

Healthy dextrals underwent fMRI during a task of graphesthesia requiring detection of any number written consecutively from an otherwise random number sequence. Test conditions included (1) focus on unilateral right hand stimuli, (2) focus on unilateral left hand stimuli, (3) focus on right hand only during bilateral hand stimulation, (4) focus on left hand only during bilateral hand stimulation, and (5) rest. Attention to unilateral hand stimulation produced bihemispheric activation with minimal or no activation of ipsilateral primary sensorimotor region. Attention to unilateral left hand stimuli resulted in more activation than attention to unilateral right hand stimuli. Stimulation of the nonattended hand activated the contralateral somatosensory area, but to a lesser spatial extent than attended stimuli. Comparing focused attention to the left versus right side during identical sensory inputs (i.e., bilateral hand stimulation), focused attention to the right hand increased activation in the left somatosensory region, but focused attention to the left hand increased activation in both cerebral hemispheres. Thus, focused attention to unilateral somatosensory stimuli produces bilateral cerebral activation, but the increase in blood flow is greater in the contralateral hemisphere. Unattended stimuli activate the contralateral primary somatosensory area. Left/right asymmetries were demonstrated consistent with cerebral lateralization.

Adult↗

Influence of segmental and extra-segmental conditioning, stimuli on cortical potentials evoked by painful electrical stimulation.

This study evaluated the effects of two different types of segmental/extra-segmental conditioning stimuli (tonic muscle pain and non-painful vibration) on the subjective experience (perceived pain intensity) and on the cortical evoked potentials to standardized test stimuli (cutaneous electrical stimuli). Twelve subjects participated in two separate sessions to investigate the effects of tonic muscle pain or cutaneous vibration on experimental test stimuli. The experimental protocol contained a baseline registration (test stimuli only), a registration with the test stimuli in combination with the conditioning stimuli, followed by a registration with the test stimuli only. In addition, the effects of the conditioning stimuli were examined at two anatomically separated locations (segmental and extra-segmental). Compared with the test stimulus alone, the perceived pain intensity and peak-to-peak amplitudes of the evoked potentials were unchanged in the presence of non-painful conditioning stimuli at either location. In contrast, a significant decrease of the perceived pain intensity and peak-to-peak amplitudes was found in the presence of painful conditioning stimuli at the extra-segmental sites. Moreover, the topographic maps of the 32-channel recordings suggested that the distribution of the scalp evoked potentials was almost symmetrical around the vertex Cz in the baseline registration. The evoked potentials were generally decreased during hypertonic saline infusion at the extra-segmental sites, but the distribution of the topographic maps did not appear to change. Vibration has previously been shown to inhibit pain, but in the present study the perceived intensity of phasic painful electrical stimuli was unchanged. The reduced perceived pain intensity and the smaller peak-to-peak amplitude of the evoked potential in the presence of extra-segmental conditioning pain are in accordance with the concept of diffuse noxious inhibitory control.

Adult↗

Dopamine inhibition of superoxide anion production by polymorphonuclear leukocytes.

To examine the modulatory effects of catecholamines on the respiratory burst in polymorphonuclear leukocytes (PMNs), dopamine was tested for its capacity to modify the superoxide anion (O2-) production by PMNs under their stimulation with several stimuli. Dopamine inhibited the O2- production by PMNs when PMNs were stimulated with N-formylated chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol myristate acetate, or opsonized zymosan, whereas dopamine did not alter the PMN mobility. The values of percentage inhibition of the O2- production by FMLP-stimulated PMNs were 57% under treatment with 10(-5) mol/L and 83% with 10(-4) mol/L of dopamine. Isoproterenol also inhibited PMN O2- production in response to FMLP. Although a beta-adrenergic blockade, propranolol, diminished the isoproterenol-induced inhibition of the O2- production, it did not affect the inhibitory effect of dopamine. The increase in intracellular cyclic AMP levels in dopamine-treated PMNs was much smaller than the increase in isoproterenol-treated cells. Furthermore, dopamine inhibited the reduced nicotinamide-adenine dinucleotide phosphate-dependent O2- production by subcellular particles. These results indicate that dopamine inhibits PMN O2- production through its effect on PMN reduced nicotinamide-adenine dinucleotide phosphate-oxidase system rather than through its beta-adrenergic action.

Chemotaxis, Leukocyte↗

Effects of different sexual stimuli on oxytocin release, uterine activity and receptive behavior in estrous sows.

This study was designed to assess effects of exogenous oxytocin (OT) on uterine activity, and to compare three different sexual stimuli in their effects on OT release, uterine activity and receptive behavior in estrous sows. Uterine activity was recorded nonsurgically, by transcervical insertion of an open-end catheter into the caudal part of the uterine lumen. After recording spontaneous uterine activity, exogenous OT was administered (Experiment 1), or one of the following stimuli was applied to the sow (Experiment 2): tactile stimuli, i.e. manual stimulation of the sow's back and flanks, tactile stimulation in combination with boar pheromone spray (5alpha-androstenon), or tactile stimuli in the presence of a boar. Both exogenous OT and endogenously released OT increased uterine activity. The effect depended on the uterine activity before treatment, with the effect being greater in those sows with lower uterine activity before treatment. In Experiment 2, boar presence was the only stimulus that elicited a clear, surge-like release of OT, and also clearly increased uterine activity. Release of OT was not necessary for induction of receptive behavior: tactile stimulation alone and in combination with pheromone spray elicited a standing response in one third of the sows, but had no effect on OT release.

Animals↗

Differential regulation of phospholipase C-beta isozymes in cardiomyocyte hypertrophy.

Cardiac hypertrophy is a major predictor of heart failure and of morbidity and mortality in developed countries. Many hormones and growth factors induce cardiac hypertrophy via activation of members of the phospholipase C (PLC) family. The expression pattern of the PLCbeta isozyme subfamily was investigated in neonatal rat cardiomyocytes after stimulation with different hypertrophic stimuli. Under control conditions and after stimulation with norepinephrine, cardiomyocytes expressed similar amounts of PLCbeta3 mRNA. In the presence of fetal calf serum (FCS), additional expression of PLCbeta1 was induced. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) both induced a substantial increase in PLCbeta3 mRNA expression. The response to GH could not be abolished by the IGF-I receptor blocker IGF-I analogue indicating an IGF-I-independent action of GH. The upregulation of PLCbeta3 by IGF-I was abolished by preincubation of cardiomyocytes with the IGF-I receptor antagonist IGF-I analogue, the tyrosine kinase inhibitor genistein, the extracellular signal-related kinase (ERK) inhibitor PD 98059, the phosphatidylinositol-3- (PI-3) kinase inhibitor wortmannin and the p70 S6 kinase inhibitor rapamycin. Induction of the immediate early genes c-myc, c-fos, and c-jun by IGF-I was abolished by preincubation with antisense oligos against PLCbeta3. It is concluded that the expression of PLCbeta isozymes in cardiomyocytes is differentially regulated by different hypertrophic stimuli. The upregulation of PLCbeta3 by IGF-I is dependent on the activity of tyrosine kinase, ERK, PI3 kinase, and p70 S6 kinase and PLCbeta3 expression seems to be required for the induction of immediate early genes by IGF-I. The involvement of the PLCbeta subfamily in signal transduction of receptors other than G-protein-coupled receptors is suggested.

Androstadienes↗

Naloxone increases the response of growth hormone and prolactin to stimuli in obese humans.

Opiates stimulate the growth hormone and prolactin responses to stimuli in non-obese humans. Obese patients, however, show lowered growth hormone and prolactin responses and raised beta-endorphin levels. We therefore investigated the effect of the opiate antagonist naloxone on the stimulated growth hormone and prolactin secretions in a controlled double-blind study in obese patients. All patients received 200 micrograms TRH and 0.5 g/kg b.w. arginine together with 2 mg of naloxone or placebo i.v. in a randomized sequence. The TRH- and arginine-induced increases in prolactin and growth hormone were significantly greater after administration of naloxone (p less than 0.05). Naloxone also produced a significant increase in ACTH, cortisol and beta-endorphin when compared with placebo. TSH, triiodothyronine, thyroxine, insulin, glucagon and blood glucose showed no significant differences between both days of the trial. The effect of naloxone on growth hormone and prolactin secretions in obese humans can thus be regarded as a partial normalization. We therefore conclude that the hypothalamic regulatory disturbance of growth hormone and prolactin secretions in the obese could be caused by raised opiate levels.

Adrenocorticotropic Hormone↗

Tissue plasminogen activator (t-PA) is targeted to the regulated secretory pathway. Catecholamine storage vesicles as a reservoir for the rapid release of t-PA.

Tissue-type plasminogen activator (t-PA) is a serine protease that plays a central role in the regulation of intravascular thrombolysis. The acute release of t-PA in vivo is induced by a variety of stimuli including exercise, trauma, and neural stimulation. These types of stimuli also result in sympathoadrenal activation and exocytotic release of amines and proteins from catecholamine storage vesicles of the adrenal medulla and sympathetic neurons. Therefore, we tested the hypothesis that t-PA is packaged in and released directly from catecholamine storage vesicles, using several chromaffin cell sources including the rat pheochromocytoma PC-12 chromaffin cell line, primary cultures of bovine adrenal chromaffin cells, and human pheochromocytoma. t-PA was expressed in chromaffin cells as detected by Northern blotting, immunoprecipitation of [35S]Met-labeled t-PA, and specific t-PA enzyme-linked immunosorbent assay of cell homogenates. In addition, chromaffin cell t-PA was enzymatically active by fibrin zymography. To explore the subcellular localization of the expressed t-PA, PC-12 cells were labeled with [3H]norepinephrine, homogenized, and subjected to sucrose density fractionation. [3H]Norepinephrine and t-PA antigen were co-localized to the same subcellular fraction with a major peak at 1.4 M sucrose, consistent with the buoyant density of catecholamine storage vesicles. In addition, catecholamine storage vesicle lysates isolated from human pheochromocytoma tumors were enriched approximately 30-fold in t-PA antigen, compared with tumor homogenate. Furthermore, exposure of PC-12 cells or primary bovine adrenal chromaffin cells to chromaffin cell secretagogues (60 microM nicotine, 55 mM KCl, or 2 mM BaCl2) resulted in co-release of t-PA in parallel with catecholamines. These data demonstrate that t-PA is expressed in chromaffin cells, is sorted into the regulated pathway of secretion, and is co-released with catecholamines by chromaffin cell stimulation. Catecholamine storage vesicles may be an important reservoir and sympathoadrenal activation an important physiologic mechanism for the rapid release of t-PA. In addition, expression of t-PA by chromaffin cells suggests a role for this protease in the proteolytic processing of chromaffin cell proteins.

Animals↗

Neural inputs from the uterus to the paraventricular magnocellular neurons in the rat.

Extracellular action potentials were recorded from antidromically identified, tonically firing cells in the hypothalamic paraventricular nucleus (PVN) of ovariectomized, estrogen-treated female rats under urethane anesthesia. Genital or somatic sensory stimuli, or electrical stimulation of the nerves innervating the pelvis were applied. Uterine horn or vaginal distension each excited 33% of the neurons tested. Probing of the cervix had no effect. Hindpaw pinch produced excitation in 39% and inhibition in 11% of the neurons tested. Non-noxious somatic stimuli had no effect. Stimulation of the uterine afferent nerves, the hypogastric and pelvic nerves, excited 55% and 30% of the neurons tested, respectively. Stimulation of a somatic nerve of the hindleg, the sciatic nerve, activated 80% of the neurons tested. These results indicate that specific sensory afferents arrive at the PVN from the uterus; in addition, somatic afferents converge in this hypothalamic nucleus.

Afferent Pathways↗

Cortical slow negative waves following non-paired stimuli: effects of modality, intensity and rate of stimulation.

Using a simple stimulus counting task, negative after-waves following single (unpaired) stimuli were investigated under a variety of stimulus conditions. Responses were obtained to tones at 3 intensities, to light flashes at 3 intensities, and to tones at 3 rates of presentation. The acoustic stimuli led to a negative after-wave that peaked at frontal sites around 500 or 600 msec, and then trailed off to a more central scalp representation. This negative after-wave was increased in amplitude by slowing the rate of stimulus presentation. In comparison, no appreciable or sustained after-wave was elicited by visual stimuli. No significant effects in the negative after-wave were associated with intensity, either for visual or for acoustic stimuli. When analyzed by Principal Components Analysis, the negative after-waves were shown to comprise in all cases two underlying factors, although the factors contributed less to the total wave form for visual stimuli than for acoustic stimuli. Two interpretations for the negative after-wave were contrasted, one considering it to be an integral feature of the auditory evoked potential. A second interpretation, more compatible with the data obtained here, links the negative after-wave with non-specific activation processes.

Acoustic Stimulation↗

Differential behavioral responsiveness to ipsilateral and contralateral visual stimuli produced by unilateral rewarding hypothalamic stimulation in the rat.

Rats were trained to respond to a visual cue signalling availability of brain reward on the left or the right side of a small chamber. Most of the rats began to respond more accurately to the visual cue presented on the side contralateral to brain stimulation than to the ipsilateral cue as the training progressed. The facilitation of the rat's response to the contralaterally presented visual cue was more evident when tested with visual cues presented simultaneously in both ipsilateral and contralateral sides. However, when tested with visual cues removed from both sides, this tendency became unclear. Additionally, monocular training gave evidence of identifying the visual cue ipsilateral to the open eye, irrespective of the electrode side. The results are interpreted as signifying that the ipsilateral hemisphere is activated by the brain stimulus and leads to improved discrimination of the contralateral visual cue because the visual system in the rat is crossed.

Animals↗