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Effects of nitric oxide availability on responses of spinal wide dynamic range neurons to excitatory amino acids.

The role of nitric oxide (NO) in responses of spinal dorsal horn neurons to excitatory amino acids and to cutaneous mechanical stimuli was examined. Extracellular recordings were made from wide dynamic range neurons excited with iontophoretically applied excitatory amino acid agonists, N-methyl-D-aspartate (NMDA) and (R,S)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) or kainic acid. Nitric oxide availability was decreased by iontrophoretic application of NO synthase inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) or L-N5-(1-iminoethyl)ornithine (L-NIO), or elevated by the NO donating compound, S-nitroso-N-penicillamine (SNAP). When cells were excited with successive application of NMDA and non-NMDA excitatory amino acid receptor agonists, application of NO synthase inhibitors led to a decrease in responses to NMDA in 60% of neurons. In more than a third of the cells tested, inhibition of NO synthase caused reciprocal changes in responses to glutamate receptor agonists: NMDA-evoked responses were significantly decreased whereas responses to the non-NMDA receptor agonists (AMPA or kainic acid) were increased. Application of the NO donating compound, S-nitroso-N-penicillamine, revealed an opposite tendency, increasing responses to NMDA in more than half of the neurons tested. In approximately 40% of the cells, reciprocal changes in responses to excitatory amino acid receptor agonists of NMDA versus non-NMDA types were observed after application of S-nitroso-N-penicillamine, such that the increase in NMDA responses was accompanied by decreases in the responses to kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

Transient spinal cord ischemia induces temporary hypersensitivity of dorsal horn wide dynamic range neurons to myelinated, but not unmyelinated, fiber input.

1. The activity of 197 single dorsal horn neurons was recorded extracellularly in the spinal cord of decerebrate, spinalized, unanesthetized rats. The response properties of 174 wide dynamic range (WDR) neurons to electrical, mechanical, and thermal stimulation in three groups of rats were studied:normal, 1-4 days after transient spinal cord ischemia induced photochemically by laser irradiation when the rats exhibited behavioral hypersensitivity to mechanical stimuli (allodynia), and 10-20 days after spinal ischemia when the allodynia had ceased. 2. In normal rats, the responses of dorsal horn WDR neurons to suprathreshold electrical stimulation of their receptive fields consisted of a short-latency (A) and a long-latency (C) response. In 77% of the neurons (57/74), there was a separation between the A- and C-fiber responses. The response threshold (defined as 20% increase in neuronal discharges above background activity) to mechanical stimulation applied with calibrated von Frey hairs was 13.8 g, and the discharges of these neurons to graded stimulation increased linearly. 3. In 68% of WDR neurons in allodynic rats (38/56), the response to suprathreshold electrical stimuli was a single burst with no separation between A- and C-fiber responses. The magnitude and duration of the response were significantly increased compared with those recorded in normal rats. The sensitivity of these neurons to mechanical stimulation was also greatly increased, expressed by a lowered threshold (2.1 +/- 0.3 g, mean +/- SE) and a shift to the left of the nonlinear stimulus-response curve. The background activity of the neurons and the size of the receptive fields were, however, unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Expanding the dynamic range of a lidar receiver by the method of dynode-signal collection.

A method of lidar data collection by simultaneous registration of signals from the anode and several dynodes of the photomultiplier is suggested. The dynamic range of the receiver has been extended as many as 5 orders of magnitude in the case of cloud sensing. The stable operation under strong background illumination is possible without losses in fine signal structure.

Journal Article↗

Estimates of loudness, loudness discomfort, and the auditory dynamic range: normative estimates, comparison of procedures, and test-retest reliability.

The purpose of this series of experiments was to establish normative reference values for absolute and relative judgements of loudness discomfort and for the auditory dynamic range (DR), and to evaluate intersubject variability and intra-subject test-retest reliability for the respective measures of loudness discomfort. To establish the normal auditory DR, audiometric thresholds and loudness discomfort levels (LDLs) were measured from a group of 59 normal-hearing adults without sound tolerance problems. The resulting estimates of the LDL and DR were on the order of 100 dB HL and 95 dB, respectively. A subset (n = 18) of this larger group participated in further studies in which loudness growth functions and the upper limit of the auditory DR were measured by categorical scaling judgments. The findings revealed no significant differences between the test methods for absolute (LDL) and relative (categorical scaling) judgements of loudness discomfort, intersubject variability, or intrasubject test-retest reliability, and suggest that the simple LDL estimate of loudness discomfort is an efficient and valid clinical measure for characterizing the "threshold of discomfort."

Adult↗

Objective assessment of image quality in conventional and digital mammography taking into account dynamic range.

The goal of this work is to develop a method to objectively compare the performance of a digital and a screen-film mammography system in terms of image quality. The method takes into account the dynamic range of the image detector, the detection of high and low contrast structures, the visualisation of the images and the observer response. A test object, designed to represent a compressed breast, was constructed from various tissue equivalent materials ranging from purely adipose to purely glandular composition. Different areas within the test object permitted the evaluation of low and high contrast detection, spatial resolution and image noise. All the images (digital and conventional) were captured using a CCD camera to include the visualisation process in the image quality assessment. A mathematical model observer (non-prewhitening matched filter), that calculates the detectability of high and low contrast structures using spatial resolution, noise and contrast, was used to compare the two technologies. Our results show that for a given patient dose, the detection of high and low contrast structures is significantly better for the digital system than for the conventional screen-film system studied. The method of using a test object with a large tissue composition range combined with a camera to compare conventional and digital imaging modalities can be applied to other radiological imaging techniques. In particular it could be used to optimise the process of radiographic reading of soft copy images.

Breast↗

Baclofen reverses the hypersensitivity of dorsal horn wide dynamic range neurons to mechanical stimulation after transient spinal cord ischemia; implications for a tonic GABAergic inhibitory control of myelinated fiber input.

1. In the companion paper, we described a state of hypersensitivity that developed in dorsal horn wide dynamic range (WDR) neurons in rats after transient spinal cord ischemia. Thus the WDR neurons exhibited lower threshold and increased responses to low-intensity mechanical stimuli. The response pattern of these neurons to suprathreshold electrical stimulation was also changed. Notably, the response to A-fiber input was increased. No change in response to thermal stimulation was found before and after spinal cord ischemia. 2. In normal rats, the gamma-aminobutyric acid (GABA)B agonist baclofen (0.1 mg/kg ip) administered 1-3 h before neuronal recording suppressed the responses of WDR neurons to high-intensity mechanical pressure without influencing the threshold and the responses to lower-intensity stimuli. 3. In allodynic rats, similar pretreatment with baclofen totally reversed the hypersensitivity of the WDR neurons to mechanical stimuli and normalized the response pattern of neurons to electrical stimulation. 4. The GABAA receptor agonist muscimol (1 mg/kg ip) did not influence the response of WDR neurons in either normal or allodynic animals. 5. The present results demonstrated that the GABAB agonist baclofen is effective in reversing the hypersensitivity of dorsal horn WDR neurons to low-intensity mechanical stimulation after transient spinal cord ischemia, indicating that dysfunction of the GABAergic inhibitory system may be responsible for the development of neuronal hypersensitivity. 6. It is suggested that GABAergic interneurons exert a tonic presynaptic inhibitory control, through baclofen-sensitive B-type GABA receptors, on input from low-threshold mechanical afferents, and that disruption of this control may result in painful reaction to innocuous stimuli (allodynia).

Animals↗

Improving speech audibility with wide dynamic range compression in listeners with severe sensorineural loss.

OBJECTIVE: In contrast to fitting strategies for linear amplification, which have been refined frequently for listeners with different degrees of hearing loss, we know relatively little about the effects of wide dynamic range compression (WDRC) amplification for listeners with severe auditory thresholds. The primary objective of this study was to determine if increases in audibility with WDRC amplification improved speech recognition to a comparable degree for listeners with different degrees of hearing loss. DESIGN: Listeners with mild to moderate or severe sensorineural loss were tested on recognition of vowel-consonant-vowel (VCV) syllables and sentences digitally processed with linear and WDRC amplification. The speech materials were presented under conditions of controlled audibility, in which WDRC amplification improved speech audibility over linear amplification. Presentation levels were chosen to provide equivalent increases in audibility with WDRC amplification for both listener groups. A control condition in which audibility was equated for the two amplification conditions was also included. RESULTS: Recognition results for VCV stimuli indicated that both listener groups received the same benefit from the improved audibility provided by WDRC amplification. Results for sentence recognition showed a greater benefit of WDRC amplification for listeners with mild to moderate than for listeners with severe loss. CONCLUSIONS: Increasing the amount of audible speech information with WDRC has similar effects on consonant recognition for listeners with different degrees of hearing loss. Differences in sentence recognition for listeners with different degrees of loss may be due to processing effects or to differences in available acoustic information for longer segments of WDRC-amplified speech.

Adult↗

Role of calcitonin gene-related peptide and its antagonist on the evoked discharge frequency of wide dynamic range neurons in the dorsal horn of the spinal cord in rats.

The present study was performed to explore the effect of calcitonin gene-related peptide (CGRP) and its antagonist CGRP8-37 on the evoked discharge frequency of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord in rats. Recording was performed with a multibarrelled glass micropipette and the chemicals were delivered by iontophoresis. The discharge of WDR neurons was evoked by transdermic electrical stimulation applied on the ipsilateral hindpaw. (1) Iontophoretic application of CGRP at an ejection current of 100 nA increased the discharge frequency of WDR neurons significantly. (2) Iontophoretic application of CGRP8-37 at an ejection current of 80 or 160 nA induced significant decreases in the discharge frequency of WDR neurons, but not at 40 nA. (3) Iontophoretic application of CGRP8-37 not only antagonized the CGRP-induced increase in the evoked discharge frequency of WDR neurons but also induced a significant decrease in the evoked discharge frequency of WDR neurons compared to basal levels. The results indicate that CGRP and its receptors play a facilitary role on the transmission and/or modulation of nociceptive information in the dorsal horn of the spinal cord in rats.

Animals↗

Calcitonin gene-related peptide 8-37 inhibits the evoked discharge frequency of wide dynamic range neurons in dorsal horn of the spinal cord in rats.

The present study was performed to explore the effect of calcitonin gene-related peptide 8-37 (CGRP8-37) on the electrical stimulation-evoked discharge frequency of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord in rats. The discharge frequencies of WDR neurons were evoked by transdermic electrical stimulation applied on the ipsilateral hindpaw. CGRP8-37 was applied directly on the dorsal surface of the L3 to L5 spinal cord. After the administration of 3 nmol of CGRP8-37, the evoked discharge frequency of WDR neurons decreased significantly, an effect lasting more than 30 min. The results indicate that CGRP receptors play an important role in the transmission of presumed nociceptive information in the dorsal horn of the spinal cord.

Animals↗

Extending the dynamic range of flame atomic absorption spectrometry: a comparison of procedures for the determination of several elements in milk and mineral waters using on-line dilution.

Three approaches based on continuous flow methodology are assessed for the purpose of extending the dynamic range of flame atomic absorption spectrometry. The determination of several elements in infant liquid and powdered milk and water samples is used to check the performances of the manifolds. Two of the systems are fully computer-controlled and permit a calibration graph to be obtained by using a single standard solution. The results confirm that continuous flow methodology is a reliable alternative to the time-consuming common dilution procedures based on glassware. Since the systems are versatile and permit a wide range of degrees of dilution to be obtained, they can be easily adapted for the automated or semi-automated analysis of other liquid samples which are too concentrated to be aspirated directly into the atomic absorption spectrometer.

Journal Article↗

Wide dynamic range germanium detector for perturbation crystallography.

An IR detector based on a cooled germanium photodetector has been tested for applications in X-ray diffraction. The detector can be used simultaneously in photon-counting mode and current mode giving a dynamic range from < 1 to 10(9) photons s(-1). Since germanium is used as the photodetector, its efficiency at energies above 25 keV is much better than the silicon equivalents. The detector proved to be highly linear both in the low-flux region (< 10(5) photons s(-1)) where photon counting is used and in the high-flux region (> 10(5) photons s(-1)) where the detector is run in current mode. The response time of the detector is of the order of 1 mus, making it suitable for studies in perturbation crystallography, especially when coupled to a lock-in amplifier. As an example, the shift of a reflection of LiNbO(3) induced by an external electric field was determined with the germanium detector and lock-in amplifier.

Journal Article↗

Wide dynamic range but not nociceptive-specific neurons encode multidimensional features of prolonged repetitive heat pain.

1. To better characterize temporal and spatial mechanisms involved in the coding of prolonged nociceptive stimuli in the spinal cord, the responses of dorsal horn wide dynamic range (WDR) and nociceptive-specific (NS) neurons to prolonged, repetitive noxious heat stimuli (45-49 degrees C) were examined in unanesthetized, spinal cord transected rats. To relate these neuronal responses to conscious dimensions of pain, human subjects were presented with identical types of prolonged, repetitive stimuli, so that psychophysical ratings of pain intensity and pain unpleasantness could be compared with the magnitudes and temporal features of the responses of NS and WDR neurons. 2. WDR neurons exhibited high rates of impulse discharge throughout 45 min of repetitive nociceptive stimulation, with only partial reduction (31% decrease from peak rates) occurring after 2 min of stimulation. In sharp contrast, NS neurons stimulated under the same conditions displayed substantial reduction of firing (73% decrease from peak rates) after a brief, initial period of activity that occurred within 2 min after onset of stimulation. Psychophysical ratings of pain intensity and pain unpleasantness, like the responses of WDR neurons, did not decrease substantially from initial levels during 7 min of painful stimulation. Furthermore, these ratings remained at high levels during time periods where the impulse frequencies of NS neurons were only at 27% of maximal levels. 3. Graded nociceptive stimuli were employed to characterize the ability of WDR neurons to encode nociceptive intensity over long durations of repetitive stimulation and to delineate further the relationship between WDR and psychophysical responses. Both WDR discharge frequencies and psychophysical ratings of pain intensity and unpleasantness increased in a monotonic manner to graded increases in stimulus temperatures. 4. These results indicate that pain does not decrease substantially during the course of prolonged, repetitive nociceptive stimulation. The fact that the responses of NS neurons decline significantly, whereas both WDR and psychophysical responses do not, suggests that WDR neurons alone are sufficient to evoke both sensory intensity and affective responses to prolonged pain. Furthermore, because subjects could localize and qualitatively describe pain at times when responses of NS neurons were minimal, WDR neurons alone can encode some spatial and qualitative aspects of pain.

Adult↗

Audibility and speech perception of children using wide dynamic range compression hearing AIDS.

PURPOSE: This study examined the relation of audibility for frequency-specific sounds and the Speech Intelligibility Index (SII) to speech perception abilities of children with sensorineural hearing loss using digital signal-processing hearing aids with wide dynamic range compression. METHOD: Twenty-six children age 5-15 years with pure-tone averages (0.5, 1.0, and 2.0 kHz) from 60-98 dB HL participated. Three subgroups were created based on the compression characteristics of each hearing aid. Minimum audibility was determined using aided thresholds for frequency-modulated tones and the SII calculated at 55 and 70 dB SPL using the simulated real-ear output of the hearing aid. The Lexical Neighborhood Test (LNT; K. I. Kirk, D. B. Pisoni, & M. J. Osberger, 1995) was presented at 50 and 70 dB SPL. RESULTS: LNT scores at 70 dB SPL were significantly higher than at 50 dB SPL. Average aided thresholds at 0.5, 1.0, and 2.0 kHz were negatively correlated with LNT scores at 50 dB SPL, and SIIs at 55 and 70 dB SPL were positively correlated with LNT scores at 50 and 70 dB SPL. CONCLUSIONS: Results support using aided thresholds and speech test scores at soft to loud levels as part of the amplification fitting process.

Auditory Threshold↗

Activation of spinal wide dynamic range neurons by intracutaneous microinjection of nicotine.

Nicotine evokes pain in the skin and oral mucosa and excites a subpopulation of cutaneous nociceptors, but little is known about the central transmission of chemogenic pain. We have investigated the responses of lumbar spinal wide dynamic range (WDR)-type dorsal horn neurons to intracutaneous (ic) microinjection of nicotine in pentobarbital-anesthetized rats. Nearly all (97%) units responded to nicotine microinjected ic (1 microl) into the low-threshold region of the hind-paw mechanosensitive receptive field in a concentration-related manner (0.01-10%). Responses to repeated injections of 10% nicotine exhibited tachyphylaxis at 5-, 10-, and 15-min interstimulus intervals. Significant tachyphylaxis was not seen with 1% nicotine. All nicotine-responsive units tested (n = 30) also responded to ic histamine (1 microl, 3%) and did not exhibit tachyphylaxis to repeated histamine. However, there was significant cross-tachyphylaxis of nicotine to histamine. Thus 5 min after ic nicotine, histamine-evoked responses were attenuated significantly compared with the initial histamine-evoked response prior to nicotine, with partial recovery over the ensuing 15 min. Neuronal excitation by ic nicotine was not mediated by histamine H1 receptors because ic injection of the H1 receptor antagonist, cetirizine, had no effect on ic nicotine-evoked responses, whereas it significantly attenuated ic histamine-evoked responses in the same neurons. The lowest-threshold portion of cutaneous receptive fields showed a significant expansion in area at 20 min after ic nicotine 10%, indicative of sensitization. Responses to 1% nicotine were significantly reduced after ic injection of the nicotinic antagonist, mecamylamine (0.1% ic), with no recovery over the ensuing 40-60 min. These data indicate that nicotine ic excites spinal WDR neurons, partly via neuronal nicotinic acetylcholine receptors that are presumably expressed in cutaneous nociceptor terminals. Repeated injections of high concentrations of nicotine led to tachyphylaxis and cross-tachyphylaxis with histamine, possibly relevant to peripheral analgesic effects of nicotine.

Action Potentials↗

Map dynamic ranges versus duration of hearing loss in cochlear implantees.

In order to assess the relationship of factors such as age, cause of deafness, use of hearing aids, duration of hearing loss, and age at onset of hearing loss, with the size of map dynamic ranges (DRs), 34 postlingually and 8 prelingually deaf users of the Nucleus cochlear implant system were analyzed according to the sizes of map DRs. Lack of auditory stimulation for a longer period than 10 years might be one of the most important factors associated with a reduced map DR. Use of hearing aids was associated with larger map DRs. Small map DRs were found across a range of age, age at onset, and duration of hearing loss. Cause of deafness did not appear to be related to map DRs.

Adolescent↗

A comparison of single-channel linear amplification and two-channel wide-dynamic-range-compression amplification by means of an independent-group design.

The present study used an independent-group design to compare the benefits provided by binaural, single-channel, linear, full-shell in-the-ear hearing aids and binaural, 2-channel, wide-dynamic-range-compression in-the-canal hearing aids in groups of older hearing aid wearers. Hearing aid outcome measures were obtained at both 1-month (n = 53) and 6-month (n = 34) postfit intervals with each device. Outcome measures included multiple measures of speech-recognition performance and self-report measures of hearing aid benefit, satisfaction, and usage. Aided sound-quality measurements were also obtained. Although both devices provided significant benefits to the wearers, there were no significant differences in the benefits provided by either device at the 1-month or 6-month postfit intervals.

Aged↗

Involvement of opioid receptors in the CGRP8-37-induced inhibition of the activity of wide-dynamic-range neurons in the spinal dorsal horn of rats.

The present study was performed to explore the involvement of opioid receptors in the calcitonin gene-related peptide 8-37 (CGRP8-37, an antagonist of CGRP receptor)-induced inhibition of the activity of wide-dynamic-range (WDR) neurons in the spinal dorsal horn of rats. Extracellular recording was performed with a multibarrelled glass micropipette, and the chemicals were delivered by micro-iontophoresis. The discharge frequency of WDR neurons was evoked by subcutaneous electrical stimulation applied to the ipsilateral hindpaw. Iontophoretic application of CGRP8-37 by an ejection current of 160 nA induced significant inhibition of the discharge frequency of WDR neurons. The inhibitory effect of CGRP8-37 on the activity of WDR neurons was attenuated by later iontophoretic application of the opioid antagonist naloxone. Furthermore, the effect of CGRP8-37 was attenuated by either iontophoretic application of the kappa-receptor antagonist nor-binaltorphimine (nor-BNI) or the mu-receptor antagonist beta-funaltrexamine (beta-FNA) but not by the delta-receptor antagonist naltrindole. The results indicate that kappa- and mu-opioid receptors on the membrane of WDR neurons are involved in the modulation of CGRP8-37-induced antinociception in dorsal horn of the spinal cord in rats.

Action Potentials↗

Expanded dynamic range of fluorescent indicators for Ca(2+) by circularly permuted yellow fluorescent proteins.

Fluorescence resonance energy transfer (FRET) technology has been used to develop genetically encoded fluorescent indicators for various cellular functions. Although most indicators have cyan- and yellow-emitting fluorescent proteins (CFP and YFP) as FRET donor and acceptor, their poor dynamic range often prevents detection of subtle but significant signals. Here, we optimized the relative orientation of the two chromophores in the Ca(2+) indicator, yellow cameleon (YC), by fusing YFP at different angles. We generated circularly permuted YFPs (cpYFPs) that showed efficient maturation and acid stability. One of the cpYFPs incorporated in YC absorbs a great amount of excited energy from CFP in its Ca(2+)-saturated form, thereby increasing the Ca(2+)-dependent change in the ratio of YFP/CFP by nearly 600%. Both in cultured cells and in the nervous system of transgenic mice, the new YC enables visualization of subcellular Ca(2+) dynamics with better spatial and temporal resolution than before. Our study provides an important guide for the development and improvement of indicators using GFP-based FRET.

Animals↗