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PubMed2002

Presynaptic group III mGluR modulation of short-term plasticity in the lateral perforant path of the dentate gyrus in vitro.

Modulation of short-term plasticity by activation of group III metabotropic glutamate receptors (mGluR) was investigated in the lateral perforant path of the dentate gyrus of the rat hippocampus in vitro. Brief trains of stimulation (10 stimuli at 1-100 Hz) evoked short-term depression of field excitatory postsynaptic potentials (EPSPs), with a steady-state level of short-term depression being attained after approximately 5 stimuli. The steady-state level of depression was frequency-dependent, increasing linearly between 1 and 200 Hz. The curve relating transmitter release per unit time to frequency of stimulation increased linearly up to a limiting frequency of 20-50 Hz, and then flattened at higher frequencies. Activation of group III mGluR by the selective agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) had two distinct actions. Firstly, the test EPSP evoked at low test frequencies was inhibited, and secondly, short-term depression evoked at high frequencies was reduced in a frequency and agonist concentration-dependent manner. Short-term facilitation became prominent at high stimulation frequencies as short-term depression was inhibited by activation of group III mGluR. Activation of group III mGluR also shifted the limiting frequency to higher values.

Animals↗

PubMed2004

Effect of dry immersion in combination with stimulation of foot support zones upon muscle force-velocity characteristics.

The complex of motor disturbances arising under conditions of real and simulated microgravity that include decrease of contractile characteristics of postural muscles is likely to be a result of withdrawal of support stimuli. Artificial stimulation of support zones of feet is shown to diminish partially or prevent completely the negative effects of microgravity on the motor system. The aim of the study was to evaluate and compare the changes of contractile properties of extensors and flexors of knee joint measured in isokinetic and isotonic regimes under conditions of simulated microgravity (7 days dry immersion).

Foot↗

PubMed1995

Cortical activation with sound stimulation in cochlear implant users demonstrated by positron emission tomography.

Six postlingually deaf patients using multi-channel cochlear implants were examined by positron emission tomography (PET) using 15O-labeled water. Changes in regional cerebral blood flow (rCBF) were measured during different sound stimuli. The stimulation paradigms employed consisted of two sets of three different conditions; (1) no sound stimulation with the speech processor of the cochlear implant system switched off, (2) hearing white noise and (3) hearing sequential Japanese sentences. In the primary auditory area, the mean rCBF increase during noise stimulation was significantly greater on the side contralateral to the implant than on the ipsilateral side. Speech stimulation caused significantly greater rCBF increase compared with noise stimulation in the left immediate auditory association area (P < 0.01), the bilateral auditory association areas (P < 0.01), the posterior part of the bilateral inferior frontal gyri; the Broca's area (P < 0.01) and its right hemisphere homologue (P < 0.05). Activation of cortices related to verbal and non-verbal sound recognition was clearly demonstrated in the current subjects probably because complete silence was attained in the control condition.

Acoustic Stimulation↗

PubMed1999

Modulation of the AT2 subtype receptor gene activation and expression by the AT1 receptor in endothelial cells.

OBJECTIVE: To investigate whether angiotensin II type 2 (AT2) receptor (AT2-r) promoter activity and expression are modulated by angiotensin II (Ang II), and whether the AT1 receptor (AT1-r) is involved in this effect. DESIGN AND METHODS: Primary endothelial cells obtained from NEONATAL rat aorta, expressing both receptors, were transfected with the rat AT2-r promoter region cloned into a pCAT-reporter vector. The reporter-expression study was performed in a transient transfection assay system. Transfected cells were studied following angiotensin-converting enzyme inhibition to prevent endogenous formation of Ang II. Cells were subsequently stimulated for 6 h with Ang II, either alone or in combination with the AT1-r antagonist DuP753. AT2-r mRNA was assessed by RNase protection assay during the same pharmacological stimuli. RESULTS: Stimulation with Ang II caused an increase in promoter activity (+50%, P < 0.05 versus baseline), whereas mRNA expression was reduced by 50% (P < 0.05 versus baseline). Concomitant treatment with DuP753 and Ang II was associated with a 98% increase in promoter activity (P < 0.05 versus baseline). DuP753 also prevented the reduction in mRNA; it actually produced a 100% increase in AT2-r mRNA accumulation (P < 0.01 versus baseline). Studies with the AT2-r antagonist PD123319 indicate that the AT2-r is also involved in the regulation of AT2-r gene promoter activity. CONCLUSIONS: These data indicate that Ang II increases AT2-r promoter activity and decreases AT2-r mRNA accumulation in endothelial cells. The AT1 subtype receptor is involved in the modulation of both effects of Ang II. These findings suggest that changes in the expression of AT2 receptors may occur during treatment with AT1-r antagonists, and they indicate the existence of a cross-talk between AT1 and AT2 receptors.

Angiotensin II↗

PubMed2007

Sphingosine 1-phosphate interferes on the differentiation of human monocytes into competent dendritic cells.

Sphingosine 1-phosphate (S1P) is a lipidic messenger known to exert several physiological functions within the cell. We tested here whether the stimulation of human monocytes with different doses of S1P might interfere with their differentiation into competent dendritic cells (DC). Monocytes cultured with granulocyte macrophage colony stimulating factor, interleukin-4 (IL-4) and S1P differentiated into a DC population lacking CD1a molecules on the surface and acquired some aspects of mature DC (mDC), though in the absence of maturation stimuli. When stimulated with lipopolisaccharide (LPS), CD1a(-) DC produce high amounts of tumour necrosis factor-alpha and IL-10, but not IL-12. Accordingly, these CD1a(-) DC were not capable of stimulating allogenic T lymphocytes so well as CD1a(+) DC generated from untreated monocytes and maturated with LPS. S1P monocyte-derived DC lost their polarizing capacity abrogating the production of gamma-interferon/IL-4 by co-cultured naïve CD4(+)CD45RA(+) T cells. Our findings suggest a mechanism through which S1P can favour the development of immune-related pathological states.

Antigens, CD1↗

PubMed1972

Changes in regional blood flow and cardiodynamics evoked by electrical stimulation of the fastigial nucleus in the cat and their similarity to orthostatic reflexes.

1. Changes in regional blood flow and cardiodynamics were measured in anaesthetized paralysed cats during electrical stimulation of the rostral fastigial nucleus.2. Fastigial stimulation results in a graded, highly reproducible and stereotyped cardiovascular response characterized by (a) increased systolic, diastolic and mean arterial pressures without changes in central venous or occluded vein pressure, (b) decreased blood flow and increased vascular resistance in the axillary, renal, femoral and mesenteric arteries, increased flow without any change in vascular resistance in the common carotid artery, and increase in total peripheral resistance, (c) a small increase in heart rate and myocardial contractile force, decrease in calculated stroke volume, and no change in the cardiac output.3. Changes in regional arterial flow were abolished by transection of sympathetic nerves or blockade of alpha-adrenergic receptors by systemic administration of phentolamine.4. Changes in heart rate and myocardial contractility were abolished by stellate ganglionectomy or blockade of beta-adrenergic receptors by propranolol.5. No changes in pupillary diameter or retraction of the nictitating membrane were seen during fastigial stimulation with stimuli producing substantial changes in blood pressure.6. The fastigial pressor response represents a highly reproducible, stereotyped, graded, and differentiated pattern of activation of sympathetic preganglionic neurones.7. The pattern of cardiovascular effects of fastigial stimulation simulates the compensatory (orthostatic) reflex response to maintenance of an upright posture.8. Fastigial stimulation appears to excite the neural network subserving orthostatic reflexes.

Animals↗

PubMed2006

PGE2 stimulates human brain natriuretic peptide expression via EP4 and p42/44 MAPK.

Brain natriuretic peptide (BNP) produced by cardiac myocytes has antifibrotic and antigrowth properties and is a marker of cardiac hypertrophy. We previously showed that prostaglandin E2 (PGE2) is the main prostaglandin produced in myocytes treated with proinflammatory stimuli and stimulates protein synthesis by binding to its EP4 receptor. We hypothesized that PGE2, acting through EP4, also regulates BNP gene expression. We transfected neonatal ventricular myocytes with a plasmid encoding the human BNP (hBNP) promoter driving expression of a luciferase reporter gene. PGE2 increased hBNP promoter activity 3.5-fold. An EP4 antagonist reduced the stimulatory effect of PGE2 but not an EP1 antagonist. Because EP4 signaling can involve adenylate cyclase, cAMP, and protein kinase A (PKA), we tested the effect of H-89, a PKA inhibitor, on PGE2 stimulation of the hBNP promoter. H-89 at 5 muM decreased PGE2 stimulation of BNP promoter activity by 100%. Because p42/44 MAPK mediates the effect of PGE2 on protein synthesis, we also examined the role of MAPKs in the regulation of BNP promoter activity. PGE2 stimulation of the hBNP promoter was inhibited by a MEK1/2 inhibitor and a dominant-negative mutant of Raf, indicating that p42/44 MAPK was involved. In contrast, neither a p38 MAPK inhibitor nor a JNK inhibitor reduced the stimulatory effect of PGE2. Involvement of small GTPases was also studied. Dominant-negative Rap inhibited PGE2 stimulation of the hBNP promoter, but dominant-negative Ras did not. We concluded that PGE2 stimulates the BNP promoter mainly via EP4, PKA, Rap, and p42/44 MAPK.

Animals↗

PubMed2002

Electrical stimulation of the sural nerve partially compensates effects of central fatigue.

OBJECTIVES: Depression of motor evoked potentials (MEPs) following transcranial magnetic stimulation (TMS) may be a sign of central motor fatigue. Abnormal fatigue can be observed in MS patients. We have examined whether post-exercise MEP depression can be compensated by application of sensory stimuli prior to TMS. METHODS: We studied 15 healthy volunteers (aged 21 to 28 years) who were required to perform an exercise protocol of ankle dorsiflexion until force fell below 66% of maximum force. MEPs were recorded from the right tibialis anterior muscle. Prior to TMS, electrical stimuli were applied to the ipsilateral sural nerve with an individual interstimulus interval between 50 to 80 ms. RESULTS: MEP areas decreased after exercise. When a sensory stimulus was administered MEPs did not change. DISCUSSION: We conclude that the effects of central fatigue may be--at least partially compensated--by application of sensory stimuli. Sensory stimulation (e.g. by implantation of a neurostimulator) might be a useful therapy for abnormal central fatigue.

Adult↗

PubMed2000

Topographic organization of the human primary and secondary somatosensory areas: an fMRI study.

The topographical organization of SI and SII somatosensory areas was investigated using fMRI at 1.5 T and electrical sensory stimulation. Electrical stimuli were delivered unilaterally to the median nerve at the wrist and to the tibial nerve at the medial malleolus, during a block paradigm study. In all subjects, activation was observed, contralaterally to the stimulated side, in the post-central gyrus, in the posterior parietal cortex, in the mesial pre-frontal region and, bilaterally, in the supratemporal region at the level of the Sylvian fissure. The latter region, corresponding presumably to SII, showed a rough but clearcut topographical organization, with the median nerve areas located more posteriorly. In addition, weaker activations were observed in some subjects in the ipsilateral mesial prefrontal region and in the ipsilateral posterior parietal cortex. Information contained in the present study represent an interesting database for future investigations on the effects of sensorimotor learning in normal individuals on plastic reorganization following a lesion of the primary sensorimotor centers, i.e. in stroke patients, on the topography and balance between upper and lower limb representations in primary and secondary somatosensory cortices.

Adult↗

PubMed2001

Modification of small bowel mechanosensitivity by intestinal fat.

BACKGROUND: Lipids may exacerbate symptoms induced by gut stimuli. AIM: To determine the mechanism whereby fat exerts this effect. SUBJECTS: Twenty four healthy subjects were studied during fasting. METHODS: We measured perception (0-6 scale) in response to jejunal balloon distension and transmucosal electrical nerve stimulation; phasic stimuli (one minute) were randomly applied at five minute intervals during intestinal infusion (2 ml/min) of saline and then Intralipid 2 kcal/min (high fat; n=8 subjects), Intralipid 0.5 kcal/min (low fat; n=8), or saline (n=8). RESULTS: Intestinal lipids increased the perception of jejunal distension regardless of concentration (by 53% with high fat, 49% with low fat, and 17% with saline; p<0.05 for both fat loads). This effect could not be attributed to changes in intestinal compliance as intraballoon pressures remained unchanged during lipid infusion (2% change; NS). Sensitisation induced by lipids seemed to be specifically related to intestinal mechanoreceptors because electrical stimulation, which non-specifically activates gut afferents, was perceived equally during saline and lipid administration (10%, 11%, and 15% change during high fat, low fat, and saline, respectively; NS). CONCLUSION: Physiological amounts of lipids heighten intestinal sensitivity by modulating intestinal mechanoreceptor response.

Adult↗

PubMedDate not supplied

Vestibulo-ocular reflexes in peripheral labyrinthine lesions: II. Caloric testing.

In a group of patients with unilateral labyrinthine dysfunction, the maximal velocity of the slow component response to caloric stimulation was compared with that to horizontal vestibular rotatory stimulation by a low-frequency stimulus. It was found that the larger the magnitude of the caloric response, the larger were the gain and sensitivity of the vestibulo-ocular reflex induced by physiologic stimuli. Rotary stimulation of patients with only one functioning inner ear provides information equivalent to that obtained from caloric stimulation and allows more rigorous quantification of the state of the vestibulo-ocular reflex.

Caloric Tests↗

PubMed2000

Tactile-spatial and cross-modal attention effects in the primary somatosensory cortical areas 3b and 1-2 of rhesus monkeys.

Neuronal responses in somatosensory cortical areas 3b and 1-2 (S1) were recorded during an attention task involving cue directed selection of one of three simultaneous stimuli: dual sinewave shaped vibrotactile stimuli applied to mirror sites on both hands or a similarly timed auditory tone. The cued stimulus occurred with one of two equally probable patterns: a constant amplitude vibration or the latter with a superimposed brief sinewave amplitude pulse midway during stimulation. Uncued stimuli always contained amplitude pulses. Two monkeys signaled the absence or presence of an amplitude pulse by appropriately moving a foot pedal up or down. Cues initiated trials by marking the location where the monkey had to discriminate the stimulus pattern. Cue location and stimulus pattern varied randomly per trial. Approximately 50% of cells (44/77 in 3b and 39/77 in 1-2) had significantly different firing rates to stimulation cued to the contralateral hand relative to spatially cuing the ipsilateral hand or cross-modally the auditory stimulus. Relatively suppressed firing rates during times prior to the epoch containing amplitude pulses improved signal-to-noise ratios for responses to amplitude pulses. Instances of significant enhanced activity during and after intervals with amplitude pulses were rare and relative to suppressed activity when cues directed attention to the ipsilateral hand or auditory stimulus. The present findings suggest that attention influences even the earliest stage somatosensory cortical processing. Findings were more modest in S1 than those previously seen in S2 (Burton et al., Somatosens Mot Res 14: 237-267, 1997), which supports the concept of multistage attention processes for touch.

Acoustic Stimulation↗

PubMed1976

The role of suprachiasmatic nuclei of the hypothalamus in the production of circadian rhythm.

(1) Action potentials were recorded from single neurons in suprachiasmatic nuclei of hypothalamus in urethane anesthetized male rat. The rate of firing ranged from less than 1 to over 10/sec but was generally 4-8/sec, and it varied from one cell to another in the same animal. (2) Repetitive stimulation of optic nerve or light acting on the eye augmented the activity of approximately half of the the suprachiasmatic neurons examined (67 out of 159 cells) while 37 neurons (23%) showed clear inhibition by the same stimuli. (3) Stimulation of the suprachiasmatic nuclei strongly inhibited the electrical activity of cervical sympathetic nerves. Light or optic nerve stimulation also inhibited activity of cervical sympathetic nerves. (4) The rate of discharge of suprachiasmatic nuclei showed, at times, some short duration oscillations occurring every 3-5 min, but at other times the same neuron showed a steady low frequency of firing. (5) Projection of optic nerves to the suprachiasmatic nuclei was demonstrated by anterograde migration of horseradish peroxidase placed in the vitreous body. (6) It was suggested that light excites certain groups of neurons in the suprachiasmatic nuclei which exert inhibitory action on cervical sympathetic nerve. This, in turn, caused a reduction in norepinephrine release by nerve fibers innervating the pineal and a reduction in pineal enzyme production. Thus, neurons in these nuclei contribute to the suppression of pineal enzyme production produced by light.

Action Potentials↗

PubMed1992

The representation of prolonged and intense, noxious somatic and visceral stimuli in the ventrolateral orbital cortex of the cat.

The responses of single neurones in the ventrolateral orbital (VLO) cortex to noxious pinch, heating of the skin, twisting of the joints and distension of the gall bladder were studied in cats anaesthetized with halothane. Of 60 neurones studied, 44 responded to prolonged (greater than 10 sec) stimuli that were well within the noxious range. Neurones were relatively unresponsive to innocuous stimuli or to the transient application of noxious stimuli. Many single neurones responded to a variety of modalities of noxious stimuli (e.g., skin heating and gall bladder distension). Many neurones studied showed a fluctuating level (5-15 Hz) of ongoing spontaneous activity. Neurones responded with either an increased frequency of spikes (excitation) or an inhibition of spontaneous discharge, irrespective of the source of noxious stimulation. Noxious stimuli delivered simultaneously to two different tissues (e.g., skin and visceral) sometimes produced excitation of the neurone under study, to levels above that produced by the application a noxious stimulus to only one of the tissues. Receptive fields were often large involving both contralateral and ipsilateral areas of the body, as well as both fore and hind limbs. No evidence of somatotopic organization was obtained. The responses of some neurones outlasted the application of the stimuli by many minutes. It is concluded that single neurones in the ventrolateral orbital cortex respond to the prolonged application of intensely noxious stimuli to a variety of body tissues, in a manner that is in keeping with the involvement of this cortical area in both the physiological, autonomic and experiential components of the affective-motivational aspect of pain. Furthermore, from the consequences of lesion studies in man and animals, it is proposed that the activation of cells in the orbital cortex by a variety of noxious stimuli reflects its more general role in the development and maintenance of behaviour in response to negative reinforcement of both social and physical origins.

Animals↗

PubMed1999

Complaints of fatigue: related to too much as well as too little external stimulation?

Fatigue has been acknowledged as a widespread problem associated with a variety of factors. In the present paper, we attempt to explain fatigue complaints on the basis of Pennebaker's (1982) "competition of cues" notion. Competition of cues suggests that both extremely low and extremely high levels of external stimulation in daily life may be related to relatively higher frequencies of complaint. The dimensional structure of external stimulation is first explored and then the shape of the relation between external stimulation (i.e., stimuli perceived in daily life) and fatigue was studied in a sample of 777 general-practice patients. Other risk factors for fatigue and moderating factors are also taken into consideration. Results show that quantity and quality of external stimulation can be distinguished. Both high quantity (high "experienced overload") and low quality (low "attractiveness of external stimulation") are related to higher fatigue frequencies. "Experienced overload" is a particularly strong predictor, in addition to "perceived health" of fatigue complaints. It is concluded that the "quality-quantity model for understanding fatigue" proposed here highlights psychological factors important for any theoretical framework of fatigue.

Adolescent↗

PubMed1994

NEUROSECRETION OF CRUSTACEAN HYPERGLYCEMIC HORMONE EVOKED BY AXONAL STIMULATION OR ELEVATION OF SALINE K+ CONCENTRATION QUANTIFIED BY A SENSITIVE IMMUNOASSAY METHOD

A sandwich-type enzyme-linked immunosorbent assay (ELISA) was utilized to quantify crustacean hyperglycemic hormone (as Carcinus maenas equivalents) released by single X-organsinus gland systems of the crab Cardisoma carnifex during continuous perifusion. Basal rates of secretion (2060 pg min-1) were stable for at least 4 h. Electrical stimulation (600 stimuli in 5 min) of the axon tract increased secretion two- to threefold, but only if it resulted in neural activity that was propagated to the terminals of the sinus gland. No difference was observable when stimuli were given repetitively or as a series of trains. Perifusion with saline having ten times the normal K+ concentration augmented secretion by as much as fivefold. Augmented secretion of crustacean hyperglycemic hormone evoked by either electrical or K+ stimulation appeared abruptly but declined slowly (over tens of minutes) after stimulation was stopped. K+-evoked secretion of crustacean hyperglycemic hormone was maintained without decrement for at least 1 h. Basal secretion increased in saline from which Ca2+ had been omitted, but decreased in saline containing Mn2+. Neither electrical stimulation nor high [K+] augmented secretion in Ca2+-deficient saline or if Mn2+ was present. Introduction of Mn2+ during K+-evoked secretion immediately reduced release to unstimulated levels; secretion resumed promptly upon removal of Mn2+. Tetrodotoxin reversibly blocked both electrical and secretory responses to axonal stimulation, but it did not block basal or K+-evoked secretion. Release of crustacean hyperglycemic hormone by isolated axon terminals was augmented two- to threefold by perifusion with saline having ten times the normal K+ concentration. The responses were similar to those of the intact systems, having a rapid onset, well-maintained secretion and a long 'tail' of secretion after removal of the K+ stimulus.

Journal Article↗

PubMed1979

Frequency resonance investigation of the H reflex.

Results of a previous study demostrated transformation of the sustained activity of a muscle into rhythmic, tremor-like activity by stimulation of different motor centres. The optimum for this transformation was in the 4-7 Hz frequency band (resonance band). Sustained rhythmic stimulation with stimuli at 0.1-20 per second caused a normal frequency curve of the H reflex in subjects with intact motor systems. The resonance phenomenon of the frequency curve of the H reflex was in agreement with that found in previous studies stimulating the different motor centres. As this requires connections between spinal and higher motor centres, it is suggested that this investigation is appropriate for a detailed functional study of spinal cord lesions.

Electric Stimulation↗

PubMed1995

Noxious stimuli induce an N-methyl-D-aspartate receptor-dependent hypersensitivity of the flexion withdrawal reflex to touch: implications for the treatment of mechanical allodynia.

Primary C-fiber afferents can induce a state of increased excitability in spinal cord neurons amplifying their responsiveness to noxious and innocuous stimuli--the phenomenon of central sensitization. We have examined whether the hypersensitivity to low-intensity stimuli (mechanical allodynia) evoked by C-afferent conditioning inputs is NMDA receptor dependent. The enhancement by C-afferent conditioning stimuli of the normally low or absent cutaneous touch-evoked responses of posterior biceps femoris/semitendinosus flexor motoneurons in the decerebrate-spinal rat has been used as a model of touch-evoked allodynia. Three different noxious conditioning stimuli (electrical stimulation of the sural nerve at C-fiber strength, cutaneous application of mustard oil and the intramuscular (i.m.) injection of bradykinin) enhanced touch-evoked responses and decreased the threshold of the flexor reflex to mechanical stimulation. Intrathecal (i.t.) injections of NMDA (20 pmol) produced a similar effect. A non-competitive NMDA antagonist MK 801, administered prior to the conditioning input at doses that did not modify the baseline reflex, significantly attenuated both the enhancement of touch-evoked responses and the threshold decrease following the noxious conditioning stimuli. Treatment with MK 801 some time after the conditioning input when the mechanical hypersensitivity is fully established, also reduced the increased touch-evoked responses. The reduction in threshold and the increase in touch responsiveness induced by cutaneous and muscle noxious C-fiber conditioning stimuli in the rat spinal cord are, therefore, both prevented and reversed by NMDA receptor antagonism. NMDA antagonists may be potentially useful, therefore, in treating postinjury pain hypersensitivity.

Animals↗