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Odor stimuli trigger influx of calcium into olfactory neurons of the channel catfish.

Olfactory transduction is thought to be mediated by a G protein-coupled increase in intracellular adenosine 3',5'-monophosphate (cAMP) that triggers the opening of cAMP-gated cation channels and results in depolarization of the plasma membrane of olfactory neurons. In olfactory neurons isolated from the channel catfish, Ictalurus punctatus, stimulation with olfactory stimuli (amino acids) elicits an influx of calcium that leads to a rapid increase in intracellular calcium. In addition, in a reconstitution assay a plasma membrane calcium channel has been identified that is gated by inositol-1,4,5-trisphosphate (IP3), which could mediate this calcium influx. Together with previous studies indicating that stimulation with olfactory stimuli leads to stimulation of phosphoinositide turnover in olfactory cilia, these data suggest that an influx of calcium triggered by odor stimulation of phosphoinositide turnover may be an alternate or additional mechanism of olfactory transduction.

Amino Acids↗

Selective adaptation in networks of cortical neurons.

A key property of neural systems is their ability to adapt selectively to stimuli with different features. Using multisite electrical recordings from networks of cortical neurons developing ex vivo, we show that neurons adapt selectively to different stimuli invading the network. We focus on selective adaptation to frequent and rare stimuli; networks were stimulated at two sites with two different stimulus frequencies. When both stimuli were presented within the same period, neurons in the network attenuated their responsiveness to the more frequent input, whereas their responsiveness to the rarely delivered stimuli showed a marked average increase. The amplification of the response to rare stimuli required the presence of the other, more frequent stimulation source. By contrast, the decreased response to the frequent stimuli occurred regardless of the presence of the rare stimuli. Analysis of the response of single units suggests that both of these effects are caused by changes in synaptic transmission. By using synaptic blockers, we find that the increased responsiveness to the rarely stimulated site depends specifically on fast GABAergic transmission. Thus, excitatory synaptic depression, the inhibitory sub-network, and their balance play an active role in generating selective gain control. The observation that selective adaptation arises naturally in a network of cortical neurons developing ex vivo indicates that this is an inherent feature of spontaneously organizing cortical networks.

Action Potentials↗

Modulation of an inhibitory reflex in single motor units in human masseter by tonic painful stimulation.

Perioral electrical stimuli cause inhibitory reflex responses in single motor-units (SMU) and surface electromyographic (EMG) recordings from voluntary contracted human jaw-closing muscles. Tonic experimental masseter pain has recently been shown to reduce the inhibitory reflex response in surface EMG recordings but the effect on SMU activity has not been described. In this study, motor-unit action potentials were recorded with wire electrodes inserted into the left masseter in eleven subjects. The subjects kept the SMU firing rate around 10 Hz by feedback. Ninety-nine electrical stimuli were applied sequentially to the left mental nerve with increasing stimulus delays in steps of 1 ms after the preceding motor unit action potential. The inhibitory reflex in SMU was recorded before, during and after infusion of hypertonic saline (5%) into the ipsilateral masseter muscle. Spike train data were used to calculate (1) the mean pre- and post-stimulus inter-spike-intervals (ISI) in all of the 99 trials, (2) cumulative changes in firing probability, and (3) estimation of the compound inhibitory post-synaptic potential (IPSP) in the masseter motoneuron. Tonic masseter pain did not change pre-stimulus SMU firing characteristics but the mean ISI for the first post-stimulus discharge (158.2+/-9.2 ms) was significantly decreased compared to the pre-pain (175.8+/-11.3 ms, P<0.05) and post-pain conditions (172. 6+/-11.6 ms, P<0.05). The post-stimulus firing probability was significantly increased and the relative amplitude of the estimated IPSP significantly decreased during tonic masseter pain compared to pre-pain and post-pain conditions. In conclusion, this study indicates that tonic masseter pain has a net excitatory effect on the inhibitory jaw-reflexes, which could be mediated by presynaptic mechanisms on the involved motoneurons.

Adult↗

Effect of orosensory stimulation on postprandial thermogenesis in humans.

This study assessed the effects of orosensory stimulation by equipalatable stimuli that differed in macronutrient content (lipid and carbohydrate) on postprandial thermogenesis. Sixteen healthy, normal-weight adults (eight males, eight females) participated in six test sessions conducted weekly. The test sessions were administered randomly after overnight fasts and included: ingestion of 50 g of butter in capsules (to avoid oral stimulation with lipids) and 500 ml of water in 15 min followed by no oral stimulation or oral stimulation with a cracker or one of the following foods on a cracker-butter, unsaturated fatty acid (UFA) margarine, jelly, UFA margarine+jelly. Sensory stimulation entailed masticating and expectorating approximately 5.0 g samples of each stimulus every 3 min for 110 min. Blood was drawn immediately after preload ingestion and at minutes 35, 85, 200, 320, and 440 postloading and was analyzed for insulin, glucagon, and glucose. No significant treatment differences were observed for thermogenesis or oxidation of carbohydrate or lipid. Insulin, glucagon, and glucose concentrations were not different between treatments. These data suggest that orosensory stimulation with stimuli differing in lipid and carbohydrate content, but rated similarly in palatability, does not elicit an increased or differential diet-induced thermogenic response.

Adolescent↗

Is V1 necessary for conscious vision in areas of relative cortical blindness?

Visual field defects result from postgeniculate lesions. It is generally assumed that absolute defects are caused by total destruction or denervation of primary visual cortex (V1) and that the degraded but conscious vision that remains or returns in relative or partial defects is mediated by compromised V1 cortex that retains a sufficiently large population of functional neurons. We here report the results of three patients with long-standing postgeniculate lesions who underwent functional magnetic resonance imaging while their partial defect was stimulated with high-contrast reversing checkerboard stimuli. Although the stimulation evoked conscious visual impressions in all three, in only one patient did it activate perilesional V1. In the other two we found no evidence for perilesional activation, indicating that some conscious vision may return in the absence of functional ipsilesional V1.

Adult↗

TRPV4.

TRPV4 is a non-selective cation channel subunit expressed in a wide variety of tissues. TRP channels are formed by a tetrameric complex of channel subunits. The available evidence suggests that TRPV4 cannot form heteromultimers with other TRPV isoforms, and that TRPV4-containing channels are homotetramers. These channels have a characteristic outwardly rectifying current-voltage relation, and are 5-10 times more permeable for Ca2+ than for Na+. TRPV4 can be activated by a wide range of stimuli including physical (cell swelling, heat, mechanical stimulation) and chemical stimuli (endocannabinoids, arachidonic acid, and, surprisingly, 4alpha-phorbol esters). Activation by swelling and endocannabinoids involves cytochrome P450 epoxygenase-dependent arachidonic acid metabolism to the epoxyeicosatrienoic acids (EETs). Heat and 4alpha-phorbol esters also seem to share a common mechanism of activation, but the endogenous messenger involved in the response to heat has not yet been identified. Ca2+ acting from the intracellular side can have both potentiating and inhibitory effects on channel activity and is involved in channel activation and inactivation. Given its wide expression and the variety of activatory stimuli, TRPV4 is likely to play a number of physiological roles. Studies with TRPV4(-/-) mice suggest a role for the channel in the regulation of body osmolarity, mechanosensation, temperature sensing, vascular regulation and, possibly, hearing.

Animals↗

Reflex and cortical responses to dental stimuli.

Tooth pulp stimulation may evoke reflex responses in the orbicularis oculi, temporal, masseter and retronuchal muscles, which may to a varying degree contaminate the cortical evoked responses. The use of repetitive stimulation reduces the amplitude of the cortical responses but avoids the onset of the majority of the muscle reflexes. The appearance of a silent period in the temporal muscle is hard to avoid and it alters the signal recorded from S1 for the first 60-70 msec. In the center-posterior leads, more protected from the EMG signal of the temporal muscle, a first negative deflection is recorded at 43 msec in 60% of subjects.

Cerebral Cortex↗

Phosphene threshold as a function of contrast of external visual stimuli.

Transcranial magnetic stimulation (TMS) of the occipital lobe is frequently used to induce visual percepts by direct stimulation of visual cortex. The threshold magnetic field strength necessary to elicit a visual percept is often regarded as a measure of electrical excitability of visual cortex. Using single-pulse TMS during visual motion stimulus presentation, we investigated the relationship between different degrees of visual cortical preactivation and cortical phosphene threshold (PT). The two possible, mutually exclusive, predictions on the outcome of this experiment were that a) PT increases with stronger preactivation because of a decrease in the signal-to-noise ratio, or b) that PT decreases with increased preactivation because of the increase in neuronal response towards some threshold. PTs for single-pulse stimulation of the occipital lobe were determined for eight subjects while they passively viewed a horizontally drifting luminance-modulated sinewave grating. Gratings used were of four different luminance contrasts while the spatial and temporal frequencies remained constant. PTs were shown to increase significantly as the background grating increased in contrast. These results suggest that the neural activity underlying the perception of a phosphene can be considered a type of signal that can be partially masked by another signal, in this case the visual cortical activation produced by passive viewing of drifting gratings.

Adult↗

Inhibition versus facilitation of the reflex responsiveness of identified wrist extensor motor units by antagonist flexor afferent inputs in humans.

The question of whether Ia reciprocal inhibition might depend on the motor task and on the type of motor unit activated was investigated in the human extensor carpi radialis muscles. Ia reciprocal inhibition induced by stimulating the median nerve (conditioning stimulation) was estimated by measuring the changes in the firing probability of 37 extensor motor units in response to the radial nerve stimulation (100 test stimuli) delivered 1 ms after the conditioning stimulation. Six subjects were asked to perform a task consisting of either selectively contracting their wrist extensor muscles or co-activating their wrist and finger antagonist muscles by clenching their hand around a manipulandum. In the control recordings (test stimulation alone), the mean response probability of the 37 motor units was found to be greater during hand clenching. The motor units were identified on the basis of their force thresholds, their macro-potentials, and their twitch contraction times. The data obtained in the control recordings were consistent with the size principle. In the recordings where the responses were conditioned by applying median nerve stimulation, the response probability of the motor units with low force thresholds, small macro-potential areas, and long twitch contraction times tended to decrease, in line with the presence of Ia reciprocal inhibition, whereas the response probability of the motor units with higher force thresholds, larger macro-potential areas, and shorter twitch contraction times tended to increase. The median nerve stimulation may therefore have altered the efficiency with which the extensor Ia inputs recruited the homonymous motoneurones in the pool. The flexor group I afferents activated while the median nerve was stimulated had inhibitory effects on the slow contracting motor units, and facilitatory effects mainly on the fast contracting motor units. Both of these effects were stronger during hand clenching, in which the numerous cutaneous receptors of the palm and fingertips are liable to be activated. Besides their own effects on the excitability of the various types of motor units, cutaneous inputs are known to potentiate the Ib interneurones. In addition, the effects of the conditioning stimulation were superimposed on the tonic activity of the Ia and Ib afferents from the flexor wrist and finger muscles. This may explain why both the inhibitory and facilitatory effects of the median nerve stimulation were enhanced during hand clenching.

Action Potentials↗

Regulation of slow potential shifts in nucleus reticularis thalami by the mesencephalic reticular formation and the frontal granular cortex.

Novel stimuli or electric stimulation of the mesencephalic reticular formation (MRF) produced large positive slow potentials (SPs) in rostral nucleus reticularis thalami (RVA) that accompanied the negative SPs known to occur in frontal cortex. SP durations (20-30 sec) were similar to the periods of unit inhibition that occur in RVA following MRF stimulation. Trains of 8 c/sec medial thalamic stimuli produced phasic negative SPs in RVA similar in duration to the intervals of unit excitation that follow each stimulus pulse. These results suggest that the polarity and duration of the SPs in RVA reflect changes in excitation of the underlying neurons. Direct activation of a specific region of RVA produced complete inhibition of visual cortex responses evoked by optic tract stimuli, a finding which suggests that RVA has an inhibitory action on the thalamus. A tone reinforced by electric shock also elicited SPs in frontal cortex (negative) and RVA (positive). In contrast to the long duration of the MRF- or novelty-elicited SPs, the durations of the conditioned SPs were phasic and were regulated by the tone--shock interval. Bilateral cryogenic blockade of the interconnections between the frontal cortex and medial thalamus abolished SPs of all origins in the frontal cortex. The blockade also abolished conditioned SPs in RVA, but did not affect the MRF-elicited ones. Thus, the subcortical SPs that accompany orienting to novel stimuli are distinct from those which occur during the higher cognitive process of conditioned expectancy and require the integrity of the mediothalamic-frontocortical system.

Animals↗

Observations upon the evoked responses to natural vestibular stimulation.

Repetitive rotational stimuli simulating natural head movements have been applied to the study of the vestibular evoked response in normal subjects and 12 patients with complete loss of vestibular function. Special precautions were taken to eliminate all possible sources of artefacts, in particular, all eye movements were restrained by requiring the subject to fixate upon a target light attached to the rotating chair throughout the course of the test. With a stimulus of 2 sec duration the typical response took the form of a slow negative wave with a mean peak amplitude of approximately 24 microV and maximally recorded from the vertex. It was characteristically absent in the patient group. Occasionally, both in normal subjects and patients it was preceded by a long latency complex thought to be non-vestibular in origin. Tests carried out both in total darkness and in the light show a statistically significant increase in the potential in the latter condition indicating an influence of the optokinetic effect exerted by the visual surround. Further studies have explored the phase changes brought about by varying the amplitude and duration of the stimulus. These have revealed certain parallels in the results of recent animal experimental studies.

Adult↗

Effects of superior colliculus lesions on rats' orienting and detection of neglected visual cues.

Superior colliculus lesions generally result in a deficit in visual orienting described as sensory neglect. This observation was confirmed in this study: Rats with lesions did not orient to some stimuli that intact rats readily oriented to. However, rats with lesions did orient to stimuli that the intact rats treated as more salient. Also, when the less salient stimuli signaled aversive stimulation, the rats with lesions detected these stimuli. These findings suggest that superior colliculus lesions do not affect the detection of visual stimuli that have been neglected.

Animals↗

Vegetative state and responses to sensory stimulation: an analysis of 24 cases.

A meta-analysis was performed on data from 24 single-case experimental studies evaluating the immediate effects of sensory stimulation treatment on patients in vegetative state following traumatic brain injury. Response to treatment was evaluated by time sampling behaviour pre- and post-treatment, and examining for changes in behaviour that suggested increased arousal. In this analysis the relative effectiveness of different treatment protocols was examined. The effects of variables such as age, gender and time since injury on magnitude of behaviour change was examined; also whether there was a relationship between response to treatment and outcome in terms of whether patients emerged from vegetative state or not. Analyses showed that multimodal stimulation produced greater behavioural changes than unimodal stimulation, and the use of personally salient stimuli in multimodal stimulation the greatest changes of all. Age and gender both showed effects on the magnitude of the behaviour change, but time since injury did not. Patients who did not emerge from the vegetative state were no less likely that those who did to produce statistically significant changes in behaviour in response to treatment. The paper includes a discussion of general issues concerning vegetative state.

Adolescent↗

The role of Na(+)-Ca2+ exchange in paired pulse potentiation of ferret ventricular muscle.

1. Stimulation of cardiac muscle with pairs of stimuli ('paired pulse stimulation') results in a large inotropic effect and experiments have been carried out on ferret ventricular muscle to investigate the underlying mechanism. 2. Aequorin was used to measure sarcoplasmic Ca2+ in papillary muscles. During paired pulse stimulation the first aequorin light transient (i.e. Ca2+ transient) and contraction of the pair increased in amplitude, whereas the second aequorin light transient and contraction were small. When the interval between the pair was decreased, the second aequorin light transient and contraction of the pair were smaller, but the increase in the first aequorin light transient and contraction was greater. 3. The relationship between contraction and the aequorin light transient was the same during paired pulse stimulation and on raising the bathing Ca2+ concentration. It is concluded that there was no change in the myofilament sensitivity to Ca2+ during paired pulse stimulation. 4. The increase in the aequorin light transient and contraction during paired pulse stimulation was prevented by ryanodine, an inhibitor of the sarcoplasmic reticulum (SR). 5. During paired pulse stimulation of ventricular myocytes there was little change in the first action potential of the pair, but the second action potential was shorter than control when the interval between the pair was short. During paired pulse stimulation of ventricular myocytes under voltage clamp control there was little change in the first Ca2+ current (iCa) of the pair, but the second iCa was smaller than control when the interval between the pair was short. Because paired pulse potentiation was greatest when the interval between the pair was short, it is concluded that paired pulse potentiation was not the result of a prolongation of the action potential or increase in iCa. 6. During paired pulse stimulation of ventricular myocytes under voltage clamp control the increase in contraction was greater, the more positive the membrane potential during the second pulse of the pair. This voltage dependence is consistent with a role for the Na(+)-Ca2+ exchanger in paired pulse potentiation. 7. During paired pulse stimulation of ventricular myocytes under voltage clamp control, changes in putative Na(+)-Ca2+ exchange current were observed consistent with a decrease of Ca2+ efflux (or increase of Ca2+ influx) via the exchanger during the second pulse of the pair. 8. A computer model of excitation-contraction coupling (Harrison, McCall & Boyett, 1992) has been used to simulate paired pulse stimulation and the results described above.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Age differences in processing relevant versus irrelevant stimuli in multiple-item recognition learning.

Age differences in the processing of relevant stimuli were examined under two levels of irrelevant stimulation. The relevant stimuli were the right words of a multiple-item recognition learning task; the two levels of irrelevant stimulation were provided by the pairing of one wrong word (two-alternative items) versus three wrong words (four-alternative items) with each right word. Elderly subjects were inferior to young adults in the learning of four-alternative items, but not in the learning of two-alternative items. This finding supports the hypothesis, derived from previous research on perceptual tasks, that elderly adults direct greater amounts of attention to irrelevant stimuli than do young adults, thus reducing the amount of processing available for the accompanying relevant stimuli. However, despite their presumed greater attention to irrelevant stimuli, elderly subjects recognized fewer individual wrong words on a subsequent memory test than did young adults. This age-related effect was interpreted in terms of depth of processing theory.

Adult↗

Modulation of perception and neurophysiological correlates of brief CO2 laser stimuli in humans using concurrent large fiber stimulation.

It has been postulated that peripheral large fiber stimulation could modulate pain perception, probably by gating the input from AS-and C-fibers. The present study examined the effects of concurrent large fiber stimulation on the perception and neurophysiological correlates of brief CO2 laser stimuli known to activate A- and C-nociceptor endings selectively. Four test stimuli of brief non-painful and painful CO2 laser pulses (duration 50 ms; diameter 5 mm; intensity range 0.116-0.212J) were delivered at random every 5-10s on the dorsum of the left forearm of ten healthy subjects. Large fiber stimulation was performed by a dynamic soft brush applied either adjacently to test stimuli (segmental brush condition) or on the dorsum of the contra-lateral foot (extrasegmental brush condition). Perception, reaction time (RT) and laser-evoked potentials (EPs) were examined for conditions with brush and without brush (control condition). The signal detection theory (SDT) was used to evaluate the discrimination performance and the decision criterion. During extrasegmental brushing, these variables were unaffected as compared with control conditions. During segmental brushing, the absolute detection threshold increased, the probability of detection decreased and the RT increased. Interestingly, the stimulus-response curve of detected stimuli and late LTPs did not change significantly. SDT analysis showed that segmental brushing did not change the discrimination performance or sensitivity but increased significantly the subject's decision criterion for reporting sensation. It was concluded that segmental brushing acted primarily at supra-spinal levels and not by gating the input from small primary afferents activated selectively by brief CO2 laser stimuli.

Adult↗

Pain suppression by peripheral nerve stimulation. Part I. Observations with transcutaneous stimuli.

A systematic, strict appraisal was made of 100 patients, after preliminary clinical trials suggested that some patients with pain could be helped by peripheral nerve stimulation. Transcutaneous stimulation of different nerve trunks was done with a special electrical stimulation device with various selected electrical parameters. More than half of the patients experienced some relief; in many, this effect was obtained by stimulating nerves distant from the area of referred pain. Pain relief lasted for varying periods after stimulation. The maximum benefit was noticed after certain specific parameters were reached for each patient. A few patients had response decay, gain or worsening. Results differ to some degree from previous reports. The results seem encouraging for the treatment of certain forms of intractable pain.

Adolescent↗