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PubMed1986

Discharge patterns of motility-regulating neurons projecting in the lumbar splanchnic nerves to visceral stimuli in spinal cats.

Reflexes in visceral preganglionic motility-regulating (MR) neurons which project in the lumbar splanchnic nerves were investigated in acutely spinalized cats. Some neurons were analyzed before and after spinalization. The stimuli used were mechanical stimulation of mucosal skin of the anus and of perianal (perigenital) hairy skin, and distension and contraction of urinary bladder and colon. Most MR neurons exhibited a reflex pattern which consists of the following components: excitation upon bladder distension, inhibition or no effect upon colon distension and excitation (or, rarely, no effect) upon anal stimulation. This is the reflex pattern of MR1 neurons. Some neurons were excited by anal stimulation but not affected from the colon and urinary bladder. Some were inhibited by anal and perianal stimulation but otherwise exhibited the reflex patterns of the MR1 neurons. Analysis of the reflexes before and after spinalization showed that, in particular, inhibition elicited by anal, perianal and bladder stimulation was abolished; inhibition elicited from the colon was enhanced after spinalization. It is concluded that the reflexes elicited in preganglionic lumbar visceral neurons by the natural stimuli probably use spinal pathways, with the afferent input occurring at the sacral spinal cord. These spinal reflex pathways are probably controlled by descending inhibitory and excitatory spinal systems from the supraspinal neuraxis.

Animals↗

PubMed1988

Idazoxan blocks the action of noradrenaline but not spinal inhibition from electrical stimulation of the locus coeruleus and nucleus Kolliker-Fuse of the cat.

The effects of idazoxan, a specific alpha 2-adrenoceptor antagonist, on spinal inhibition by administration of noradrenaline and from electrical stimulation of the dorsolateral pons were studied in 26 cats anaesthetized with sodium pentobarbitone. The excitation of dorsal horn neurons of the spinal cord by noxious heating of the skin or by impulses in unmyelinated primary afferent fibres was markedly reduced when noradrenaline was administered microelectrophoretically in the substantia gelatinosa or near cell bodies. Electrical stimulation of the region of the locus coeruleus selectively inhibited spinal nociceptive transmission when dorsal horn neurons were excited by noxious and non-noxious stimuli. In contrast to stimulation of the locus coeruleus, stimulation of the nucleus Kolliker-Fuse produced non-selective inhibition of both nociceptive and non-nociceptive responses of dorsal horn neurons of the spinal cord. Microelectrophoretic ejection of idazoxan reduced or abolished noradrenaline-induced inhibition with 19 of 20 neurons. This antagonist did not alter inhibition from stimulation of the locus coeruleus and the nucleus Kolliker-Fuse, regardless of whether it was administered microelectrophoretically (11 neurons), systemically (3 neurons) or topically (4 neurons). The results suggest that alpha 2-adrenoceptors do not mediate inhibition of spinal nociceptive transmission from electrical stimulation of the locus coeruleus and the nucleus Kolliker-Fuse. Other possibilities for the failure of idazoxan to modify inhibition from such stimulation are discussed.

Action Potentials↗

PubMed1979

Effects of stimulating in raphe nuclei and in reticular formation on response of spinothalamic neurons to mechanical stimuli.

1. The purpose of these experiments was to compare effects of electrical stimuli applied in two regions of the brain stem that are the sites of origin of descending bulbospinal systems; namely, the nucleus gigantocellularis of Brodal (7) and the nucleus raphe magnus, on the responses of lumbosacral spinothalamic neurons to mechanical stimuli. 2. In cats anesthetized with alpha-chloralose, stimulating in either of these structures with single pulses of current while the spinothalamic neuron was tonically activated by a sustained mechanical pressure resulted in an increase in the excitability of the cell followed by a prolonged suppression of its impulse activity. 3. For different neurons, the latency of the excitation ranged from 4 to 18 ms following the brain stem stimulus, while the latency of the suppression ranged from 16 to 34 ms. 4. In general, the effects of stimulating in the reticular formation and in the raphe nuclei were similar. although quantitative differences were found in the effects of each on different spinothalamic neurons. On the basis of these two studies, it is argued that the reticulospinal and raphe-spinal systems exert qualitatively similar effects on the responses of spinothalamic neurons evaluated in this experiment. 5. A comparison of the magnitudes of the suppression phase evoked from several different sites in the ipsilateral reticular formation and nucleus raphe magnus suggests that the descending systems arising from both these structures may be quite heterogeneous. 6. Stimulation of both regions of the brain stem produced a much greater suppression of the response of the spinothalamic neurons to slowly changing or sustained mechanical stimuli than to transient stimuli. It is suggested that the effects of descending systems arising both in the raphe nuclei and in the reticular formation on the responses of spinothalamic neurons to a mechanical stimulus are at least as dependent on the time course of the mechanical stimulus as they are on its intensity.

Animals↗

PubMed1996

Simultaneous independent measurement of endocytosis and exocytosis.

Studies of membrane traffic between the cytoplasm and surface of a cell suggest that membrane internalization is tightly coupled to secretion. Studies using the capacitance technique show that endocytosis can follow evoked exocytosis within a second or less. The capacitance technique, however, measures only the net change in cell surface area, and thus separating exocytosis from endocytosis requires that the two events do not overlap in time. This condition is probably met with small, brief stimuli, but during prolonged stimulation it is more likely that exocytosis and endocytosis occur simultaneously, We used FM1-43 fluorescence, which provides a cumulative measure of exocytosis, independent of endocytosis, in combination with capacitance monitoring to track unidirectional movements of membrane simultaneously and in real time in bovine adrenal chromaffin cells. We confirm that, with relatively small stimuli, exocytosis ceases before endocytosis begins (no overlap). In contrast, during prolonged stimulation, the onset of endocytosis is delayed by 2-3 min, but then the rate of endocytosis quickly grows to equal that of exocytosis. The delayed onset of endocytosis may be an emergency defence against catastrophic cell swelling.

Adrenal Cortex↗

PubMed1968

Frequencygrams of spindle primary endings elicited by stimulation of static and dynamic fusimotor fibres.

1. Frequencygrams of cat spindle primary endings, obtained by the method described by Bessou, Laporte & Pagès (1968), were elicited by the stimulation of single static and dynamic fusimotor fibres.2. Stimulation of static fibres by single stimuli may elicit: (i) no response, (ii) responses of small amplitude, (iii) responses of large amplitude with a pause after the rising phase.3. Stimulation of static fibres by repetitive stimuli gives frequencygrams resembling records of tetanic contraction of skeletal muscle. At a frequency of stimulation of 180-200/sec periodic oscillations are perceptible on the plateau of the frequencygram.4. Stimulation of dynamic fibres by single stimuli may elicit: (i) no response, (ii) responses smaller and longer than the responses given by static fibres.5. When the muscle is stretched the amplitude of the responses elicited by dynamic fibres decreases whereas the amplitude of the responses given by static fibres increases.6. Frequencygrams obtained by repetitive stimulation of dynamic fibres show periodic oscillations only at low rates of stimulation. At rates of stimulation higher than the minimal rate giving frequencygrams with a smooth contour, the amplitude of the frequencygram increases.

Animals↗

PubMed2005

Comparisons between neural response imaging thresholds, electrically evoked auditory reflex thresholds and most comfortable loudness levels in CII bionic ear users with HiResolution sound processing strategies.

CONCLUSIONS: The data collected in this study indicated that first Neural Response Imaging (NRI) thresholds had a better correlation with HiResolution most comfortable loudness (M) levels than tNRI thresholds. Electrically evoked auditory reflex thresholds (EARTs) had a higher correlation with HiResolution M levels than tNRI thresholds and a lower correlation than first NRI thresholds. NRI is a very useful method for programming the cochlear implants of young children who cannot demonstrate a reliable judgment of loudness. OBJECTIVE: To investigate how HiResolution sound processing, designed to deliver high-rate stimuli, relates to EARTs and electrically evoked compound action potential measurements produced by low-rate stimuli. MATERIAL AND METHODS: Nine profoundly hearing-impaired children and adults aged 6-29 years participated in the study. NRI responses were elicited using pulse trains consisting of biphasic pulses at a pulse width per phase of 32 micros delivered at a frequency of 30 Hz using SoundWave programming software. Stimuli were delivered to the odd electrodes (1, 3, 5, 7, 9, 11, 13 and 15) along the array. tNRI (NRI threshold) and first NRI thresholds were recorded for each stimulating electrode. "Speech bursts" stimuli used in EARTs recording were delivered to four electrodes at a time and stapedial reflexes were recorded from the impedance bridge. The M levels used were those used by each patient in their everyday HiResolution programs. RESULTS: For 8 patients (53 stimulating electrodes) the correlation between tNRI threshold and M level was r=0.675 (p=0.000) and that between first NRI thresholds and M level was r=0.741 (p=0.000). On average the M-level value was 20 CU (Current Unit) lower than the first NRI threshold value and 12 CU higher than the tNRI threshold value. The M-level patterns across the electrode array overall were similar to the tNRI or first NRI threshold patterns. For 7 patients (112 stimulating electrodes) the correlation between EART and M levels was r=0.710 (p=0.000). On average the EART value was 14 CU higher than the M-level value.

Adolescent↗

PubMed1985

Reduction of body sway by stimuli imaged within a cortical scotoma: a case study.

The reduction of body sway by visual stimulation was equally effective for stimuli imaged within a cortical scotoma or in the mirror image position in the normal visual field. The results are consistent with the concept of distinct visual orientation and discrimination modes of processing visual information, which suggests that spatial orientation functions do not necessarily involve awareness.

Adult↗

PubMed1986

Contrast enhancement in frequency spectra of cochlear microphonic responses to complex stimuli.

Cochlear microphonic responses were measured in pigeons and guinea pigs during stimulation with complex sounds. The acoustical stimuli had many component frequency spectra with a more or less undulating envelope. Enhancement of the peak-and-valley structure of the envelope occurred at high stimuli levels, especially if all frequency components in the stimulus had equal (cosine) phase. The observed effects could very well be modelled with a simple passive electronic network, as well as with an analytical expression that describes saturation of the cochlear microphonic at high stimulus levels.

Acoustic Stimulation↗

PubMed2000

Left vagus nerve stimulation suppresses experimentally induced pain.

OBJECTIVE: To test whether electric stimulation of the vagus nerve has an antinociceptive effect in humans. BACKGROUND: In a variety of animal studies, vagus nerve stimulation was shown to inhibit nociceptive behavior as well as electric responses of spinal nociceptive neurons. In humans, chronic left vagus nerve stimulation is used to treat pharmacologically refractory epilepsy. METHODS: The authors investigated experimental pain in 10 patients with seizures before and twice after implantation of a vagus nerve stimulator by using different controlled stimuli, including noxious heat, tonic pressure, and short impact. Pain was quantified on a visual analogue scale. Twelve nonepileptic age- and gender-matched individuals served as control subjects. RESULTS: Vagus nerve stimulation reduced increasing pain associated with trains of five consecutive stimuli at 1.5-second intervals ("wind-up"; p < 0.001). In a similar manner, pain on tonic pressure was reduced by vagus nerve stimulation (p < 0.03). Pain associated with single-impact stimuli as well as heat pain thresholds were unaltered under vagus nerve stimulation. Thus, vagus nerve stimulation led to pain relief predominantly in experimental procedures in which pain magnitude was amplified by central processing. The antinociceptive effect was independent of the acute on-off cycles of vagus nerve stimulation. CONCLUSIONS: Vagus nerve stimulation is effective in reducing pain in humans. In humans, the antinociceptive effect might rely on central inhibition rather than alterations of peripheral nociceptive mechanisms. These results indicate a promising, potential future role of vagus nerve stimulation in pain treatment.

Adult↗

PubMed1981

Presynaptic inhibition of transmission from identified interneurons in locust central nervous system.

1. Intracellular recordings near the output terminals of an identified interneuron (the descending contralateral movement detector, DCMD) in the locust revealed the occurrence of depolarizing synaptic potentials. These presynaptic depolarizing potentials were evoked by spikes in both DCMDs, by auditory stimuli, and by electrical stimulation of the pro- to mesothoracic connectives. The occurrence of the depolarizing potentials decreased the amplitude of the action potentials close to the output terminals. 2. The stimuli that produced depolarizing potentials in the presynaptic terminals reduced the amplitude of the monosynaptic excitatory postsynaptic potentials evoked by the DCMDs in identified follower interneurons. We conclude that at least part of this reduction in transmission from the DCMDs results from presynaptic inhibition and that the presynaptic inhibition is related to a reduction in the amplitude of the presynaptic action potentials. 3. We propose that the function of the presynaptic inhibition of the DCMDs is to ensure that the interneurons triggering a jump are never activated by the DCMDs in the absence of proprioceptive signals from the legs indicating the animal's readiness to jump.

Action Potentials↗

PubMed1990

Diaphragmatic fatigue in the rat.

We studied fatigue of rat diaphragm in response to repetitive brief and prolonged electrical stimulation of the phrenic nerve, at 0.2, 1-100 Hz. Low and high frequency of stimulation produced twitch and tetanic contractions in the rat diaphragm. A mean maximum twitch tension of 1.4 +/- 0.1 g was produced at 1 Hz, and a mean maximum tetanic tension of 5.6 +/- 0.3 g was obtained at 100 Hz (means +/- S.E., n = 8). Twitch and tetanic fatigue was produced at all frequencies of stimulations, but with different time scale, or duration, and with different number of stimuli delivered to the muscle. At low rates of stimulation, e.g. 10 Hz, fewer stimuli were needed to fatigue the muscle (3000 in 5 min), whereas at high rates of stimulation, e.g. 50 Hz, more stimuli were needed to fatigue the muscle (6600 in 2.2 min). The amplitude of the tetanic tensions elicited at 10 and 50 Hz, at the end of 5 or 2 min fatiguing stimulation, was 39 +/- 2.7% and 80 +/- 3.1% of their respective control tensions (2.8 +/- 0 2 g and 5.3 +/- 0.5 g, n = 8, P 0.001). It was concluded that fatigue in the rat diaphragm depended on the frequency and duration of stimulation as well as on the number of stimuli delivered to the muscle. Various mechanisms of muscle fatigue are described in the discussion to explain the observations made in the present investigation.

Animals↗

PubMed1984

Ensemble reactions of neurons in the reticular formation of the cat--categorization of inputs and temporal influences.

A method of recording ensemble reactions of reticular neurons was applied in anesthetized cats to obtain information about categorization of inputs and the influence of the time factor upon a pattern of responses, reactions to stimulus intensity changes and to complex stimuli, and temporal influences with their relation to plastic changes induced by iterative stimulation. In spite of some variability of the pattern of responses evoked in the reticular formation (RF) by electrical stimulation of the same source, reactions of the parenchyma of the RF differentiate heterotopic stimuli; reactions evoked from receptor areas situated closely to each other exhibited a similar pattern whereas less resemblance was found in the case of responses evoked from sources with a heterosegmental projection and from contralateral sources. Stimulus intensity changes did not influence substantially the pattern of recordings in the RF. The noticeable effect resulting from the increase of stimulus intensity was enlargement of responses. A complex stimulus (two heterotopic stimuli applied simultaneously) was manifested by a reaction which, in comparison with reactions evoked from each of both sources separately, had a different pattern. A trend of changes in the size of responses evoked in the RF by continuous stimulation (60 stimuli, 0.3 Hz) was observed only in some cases. Abrupt alterations of the stimulation rate (0.3 Hz in equilibrium 1 Hz, 0.3 Hz in equilibrium 2 Hz) resulted in a prompt change in responses. With constant stimulation conditions, this activity was fairly constant with an absence of trends. Persistent changes were observed only in a minority of cases. The neuronal apparatus of the RF computes ongoing effects on the basis of ability to discriminate different inputs and to readily change its function. The extent to which the RF holds information about the antecedent "history" of its functioning and the extent to which intrinsic mechanisms of the RF by itself are responsible for behavioral habituation remains problematical.

Animals↗

PubMed1983

Reticulospinal regulative commands in the cat evoked at the segmental level: the effect of repetitive stimuli.

The reticular formation of the brain stem participates in the neuronal activity which is evoked by an unexpected or intense stimulus and results in a generalized (startle) reaction of the organism. If this reaction is evoked from the segmental receptor level, it comprises a spino-reticulo-spinal (i.e. spino-bulbo-spinal--SBS) reflex. Repetition of the stimulus leads to a habituation of the startle reaction. We studied the effect of repetition and the frequency of the stimulus on the SBS reflex response in somatic nerves of chloralose-anaesthetized cats. A series of 60 stimuli with a low stimulus repetition frequency (less than or equal to 0.2 Hz) did not induce any trend in changes in SBS responses. Frequencies of 0.5 and 1 Hz in some cases led to sensitization or depression of SBS discharges, while higher frequencies (2 and 5 Hz) caused a depression and a decrease in the incidence of SBS response in efferent discharges in every case. These changes occurred promptly (in the course of 5-15 stimuli at a given frequency); continued stimulation did not induce a habituation trend in the changes of SBS responses. When a series of stimuli with a frequency causing a change in the functional state of the SBS system ended, SBS responses returned to control values in the course of the first 5 stimuli at the basic stimulation frequency (0.2 Hz), except for a few cases in which a persistence of the change in SBS responses was observed. The findings showed that a protracted repetition of the stimulus did not lead to the disappearance of the reticular formation reactions resulting in reticulospinal regulative commands in the form of SBS activity. The level of this activity is adapted promptly in correlation to the change in the stimulation parameters; with constant parameters, SBS activity is relatively constant.

Adaptation, Physiological↗

PubMed1986

Electrophysiological studies on the effects of intrathecal morphine on nociceptive neurones in the rat dorsal horn.

We have studied the effects of intrathecal morphine on the responses of 38 dorsal horn neurones in the intact rat under halothane anaesthesia to A and C fibre electrical stimulation and to natural stimuli applied to their receptive fields. Morphine selectively reduced the C fibre and pinch evoked activity in a dose-dependent naloxone-reversible manner with an ED50 of 7 nmoles. The 'wind-up' of neurones to repetitive stimulation was little altered except with the highest doses (50-150 nmoles) tested. By contrast, the A fibre evoked responses of the neurones were only slightly reduced by morphine and both the tactile responses and receptive field size to innocuous stimuli enhanced for certain cells. The results are discussed in relation to the spinal actions of opiates and their clinical applications.

Animals↗

PubMed1997

Gut pain reactions in man: an experimental investigation using short and long duration transmucosal electrical stimulation.

Visceral pain is a substantial, clinical problem but unfortunately few experimental models are available to study this phenomenon in man. In the present study we inserted a stimulation catheter 5-10 cm into the ileo-sigmoidostomy of nine patients. The catheter contained six small, flexible electrodes separated by 4 mm. The gut was stimulated by single burst, repeated burst (five stimuli delivered at 2 Hz), or continuous burst stimuli (4 Hz for 30, 60, 90, and 120 s). The sensation (ST), pain detection (PDT), and pain tolerance (PTT) thresholds to single/repeated burst stimuli were determined. The location/size/sensitivity of referred pain after repeated/continuous stimulation were characterized. The brain potentials to single burst stimuli and to increasing stimulus intensity were measured. ST to single burst stimuli was easy to determine (8 mA) and to reproduce. The patients found it difficult to determine the PDT and PTT to single burst stimuli, however both thresholds were easily determined for repeated burst stimuli. The pain thresholds to single burst stimuli were twice as high as the thresholds to repeated burst stimuli, indicating the importance of central temporal summation for visceral pain. Minor changes in the stimulus location resulted in changes of the referred pain projection site. The words most frequently selected (78%) from the McGill Pain Questionnaire to describe repeated burst stimulations were shooting, pricking, flashing, and boring. The amplitude of the brain potentials increased at increasing stimulus intensity. A stimulus intensity giving an initial pain rating of around 5 on a 0-10 visual analog scale (VAS) was used for continuous stimulation. A general increase of the pain intensity and the area of referred pain was found during this stimulation. It was concluded that electrical stimulation of the human gut provokes pain and especially long sequences of visceral stimuli are adequate to evoke referred pain mimicking pain profiles of pathologic origin.

Adult↗

PubMed1982

Tomographic mapping of human cerebral metabolism: auditory stimulation.

Cerebral metabolic responses to verbal and nonverbal auditory stimuli were examined, using 18F-fluorodeoxyglucose and positron CT. Twenty right-handed subjects were studied in both control and stimulated states. Monaural verbal stimuli produced diffuse metabolic changes in the left hemisphere and bilateral activation of the transverse and posterior temporal lobes. Monaural nonverbal stimulation with chords demonstrated bilateral parietotemporal activations and diffuse right greater than left frontotemporal asymmetries. Tone sequence pairs presented monaurally produced asymmetries that differed by the subject's analysis strategy. Nonanalytical, musically naive subjects had right greater than left frontotemporal asymmetries, whereas analytic or musically sophisticated subjects had an absence of right greater than left relative hypermetabolism and demonstrated left greater than right temporal asymmetries. Binaural presentation of a factual story and music produced diffuse bilateral activations of the temporal and frontal cortex. Known anatomic asymmetries of the perisylvian cortex were revealed by high-resolution tomography. These results demonstrate that metabolic responses to auditory stimuli are determined by the content of the stimulus and the analysis strategy of the subject rather than the side of stimulation. The results also demonstrate the capacity of functional imaging techniques to study the physiologic cerebral mechanisms underlying auditory processing.

Acoustic Stimulation↗

PubMed2000

Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine.

The enteric nervous system contains intrinsic primary afferent neurons that allow mucosal stimulation to initiate reflexes without CNS input. We tested the hypothesis that submucosal primary afferent neurons are activated by 5-hydroxytryptamine (5-HT) released from the stimulated mucosa. Fast and/or slow EPSPs were recorded in submucosal neurons after the delivery of exogenous 5-HT, WAY100325 (a 5-HT(1P) agonist), mechanical, or electrical stimuli to the mucosa of myenteric plexus-free preparations (+/- extrinsic denervation). These events were responses of second-order cells to transmitters released by excited primary afferent neurons. After all stimuli, fast and slow EPSPs were abolished by a 5-HT(1P) antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide, and by 1.0 microM tropisetron, but not by 5-HT(4)-selective antagonists (SB204070 and GR113808A) or 5-HT(3)-selective antagonists (ondansetron and 0.3 microM tropisetron). Fast EPSPs in second-order neurons were blocked by hexamethonium, and most slow EPSPs were blocked by an antagonist of human calcitonin gene-related peptide (hCGRP(8-37)). hCGRP(8-37) also inhibited the spread of excitation in the submucosal plexus, assessed by measuring the uptake of FM2-10 and induction of c-fos. In summary, data are consistent with the hypothesis that 5-HT from enterochromaffin cells in response to mucosal stimuli initiates reflexes by stimulating 5-HT(1P) receptors on submucosal primary afferent neurons. Second-order neurons respond to these cholinergic/CGRP-containing cells with nicotinic fast EPSPs and/or CGRP-mediated slow EPSPs. Slow EPSPs are necessary for excitation to spread within the submucosal plexus. Because some second-order neurons contain also CGRP, primary afferent neurons may be multifunctional and also serve as interneurons.

Afferent Pathways↗

PubMed1973

Some effects of inhibiting endogenous prostaglandin formation on the responses of the cat spleen.

1. Cat isolated spleens release prostaglandins into the venous effluent in response to stimuli such as nerve stimulation, noradrenaline and angiotensin II.2. The release of prostaglandins is abolished by pre-treatment of the spleen with indomethacin (0.3-5 mug/ml).3. The capsular and vascular responses to the different stimuli are augmented after inhibition of prostaglandin release.4. The prevention of prostaglandin release, as well as the augmentation of vascular and capsular responses, are reversible after indomethacin treatment is stopped.5. The role of prostaglandins as modulators of the responses to several stimuli is discussed.

Angiotensin II↗