Showing papers on "Summation published in 1994"

The N-methyl-D-aspartate receptor antagonist dextromethorphan selectively reduces temporal summation of second pain in man.

Abstract: Oral doses of dextromethorphan (DM), a common cough suppressant and N-methyl-D-aspartate (NMDA) receptor antagonist, and their vehicle control were given on a double-blind basis to normal volunteer human subjects who rated intensities of first and second pain in response to repeated painful electric shocks and repeated 52 degrees C heat pulses. Doses of 30 and 45 mg, but not 15 mg, were effective in attenuating temporal summation of second pain, a psychophysical correlate of temporal summation of C afferent-mediated responses of dorsal horn nociceptive neurons, termed 'wind-up'. By contrast, neither first nor second pain evoked by the first stimulus in a train of stimuli were affected by any of these doses of DM. These results further confirm temporal summation of second pain as a psychophysical correlate of wind-up by providing evidence that DM selectively reduces temporal summation of second pain, as has been shown for wind-up.

Electrophysiological and psychophysical quantification of temporal summation in the human nociceptive system.

Abstract: Animal experiments have shown that the nociceptive reflex can be used as an indicator of central temporal integration in the nociceptive system. The aim of the present study on humans was to investigate whether the nociceptive reflex, evoked by repetitive strong electrical sural nerve stimuli, increased when summation was reported by the volunteers. The reflexes were recorded from the biceps femoris and rectus femoris muscles in eight volunteers following a series of stimulations at 0.1, 1, 2, and 3 Hz. Each series consisted of five consecutive stimuli. Using 0.1- and 1-Hz stimulation, the reflex was not facilitated in the course of the five consecutive stimuli. Following 2- and 3-Hz stimulation, the reflex size (root mean square amplitude) increased significantly during the course of the fifth stimulus. This reflex facilitation was followed by a significant increase (summation) in the pain magnitude when compared with 1- and 0.1-Hz stimulation. Furthermore, the threshold for psychophysical summation could be determined. This threshold (stimulus intensity) decreased when the stimulus frequency (1–5 Hz) of the five consecutive stimuli was increased. The nociceptive reflex and the psychophysical summation threshold might be used to clarify and quantify aspects of temporal summation within the human nociceptive system.

Membrane properties underlying the firing of neurons in the avian cochlear nucleus

Abstract: Neurons of the avian nucleus magnocellularis (NM) relay auditory information from the VIIIth nerve to other parts of the auditory system. To examine the cellular properties that permit NM neurons to transmit reliably the temporal characteristics of the acoustic stimulus, we performed whole-cell recordings in neurons of the chick NM using an in vitro thin slice preparation. NM neurons exhibited strong outward rectification near resting potential; the voltage responses to depolarizing current steps were substantially smaller than to equivalent hyperpolarizing steps. Suprathreshold current steps evoked only a single action potential at the start of the step. In contrast, stimulation with trains of brief current pulses evoked repetitive firing that was phase-locked to the stimulus cycle. The number of action potentials evoked by the pulses during the train decreased with increasing stimulus rate. Voltage-clamp experiments revealed a rapidly activating, slowly inactivating, outward current with a threshold near - 65 mV. During depolarizing voltage steps, the outward current rose sigmoidally to a peak and then decayed slowly, reaching steady state within 5 sec. Application of 200 microM 4-aminopyridine (4-AP) reduced the peak of the outward current by 84%, leaving a small, persistent component. Under current clamp, application of 200 microM 4-AP reduced the outward rectification and increased the amplitude and duration of the action potentials. Moreover, NM neurons could no longer sustain firing during high rates of stimulation with the current pulses: increased temporal summation of the potentials caused sufficient depolarization to inactivate the sodium conductance underlying the action potential. These results suggest that the outward current is necessary for NM neurons to transmit well-timed events reliably for the duration of an acoustic stimulus.

Membrane Properties Underlying the Firing of Neurons in the Avian

Abstract: Neurons of the avian nucleus magnocellularis (NM) relay auditory information from the Vlllth nerve to other parts of the auditory system To examine the cellular properties that permit NM neurons to transmit reliably the temporal characteristics of the acoustic stimulus, we performed wholecell recordings in neurons of the chick NM using an in vitro thin slice preparation NM neurons exhibited strong outward rectification near resting potential; the voltage responses to depolarizing current steps were substantially smaller than to equivalent hyperpolarizing steps Suprathreshold current steps evoked only a single action potential at the start of the step In contrast, stimulation with trains of brief current pulses evoked repetitive firing that was phase-locked to the stimulus cycle The number of action potentials evoked by the pulses during the train decreased with increasing stimulus rate Voltage-clamp experiments revealed a rapidly activating, slowly inactivating, outward current with a threshold near -65 mV During depolarizing voltage steps, the outward current rose sigmoidally to a peak and then decayed slowly, reaching steady state within 5 sec Application of 200 PM 4-aminopyridine (4-AP) reduced the peak of the outward current by 64%, leaving a small, persistent component Under current clamp, application of 200 @A 4-AP reduced the outward rectification and increased the amplitude and duration of the action potentials Moreover, NM neurons could no longer sustain firing during high rates of stimulation with the current pulses: increased temporal summation of the potentials caused sufficient depolarization to inactivate the sodium conductance underlying the action potential These results suggest that the outward current is necessary for NM neurons to transmit well-timed events reliably for the dura

Differential ability of human cutaneous nociceptors to signal mechanical pain and to produce vasodilatation

Abstract: We investigated the ability of human nociceptive primary afferent neurons to encode mechanical pain and to produce vasodilatation. Pain was induced by shooting a light metal cylinder (0.3 g) at different velocities (6–18 m/sec) perpendicularly against the hairy skin of the hand. When single impact stimuli were applied, monotonically increasing stimulus-response functions were obtained in 10 psychophysical experiments using magnitude estimation techniques. In 35 microneurographic experiments nine unmyelinated afferents were recorded from the superficial radial nerve. All units responded readily to impact stimulation even at stimulus intensities that were not rated as painful. However, there was a close linear correlation between the number of action potentials evoked from the nociceptors and the psychophysical magnitude estimates of the perceived sensation or the stimulus intensity. This was also reflected by a corresponding increase of neurogenic vasodilatation. While two thin myelinated afferents displayed qualitatively similar responses 12 low-threshold mechanosensitive afferents (4 rapidly adapting, 5 slowly adapting type 1, 3 slowly adapting type II) failed to encode the intensity of the applied impact force and often became desensitized. This indicates that the total number of action potentials is the determinant of the magnitude of mechanical pain and the associated vasodilatation following single brief stimuli. By contrast, the close correlation between nociceptor activity and sensation changed when trains of mechanical impact stimuli (five stimuli of constant intensity, intratrain frequency of 1/32 to 2 Hz) were applied. Magnitude estimates of pain intensity were frequency dependent and stimuli with short interstimulus intervals were perceived as more painful than those delivered with long intervals. However, the total number of action potentials evoked from C-fibers was higher at longer interstimulus intervals than shorter intervals, thus yielding a negative correlation between the magnitude estimates of the perceived painful sensation and the number of action potentials elicited from nociceptive afferents. This suggests that temporal summation of the nociceptive discharge at central neurons becomes increasingly more important for the sensory discriminative experience of pain evoked by repetitive stimulation. We conclude that human nociceptive C-fibers signal brief noxious mechanical stimuli by the total number of action potentials evoked during a short period of time. However, with repetitive stimulation the total number of action potentials evoked from nociceptors is less important for evoking pain and temporal summation of the nociceptive primary afferent discharge becomes the crucial factor for signaling the magnitude of sensation.

Synaptic inhibition influences the temporal coding properties of medial superior olivary neurons: an in vitro study.

Abstract: The medial superior olive (MSO) functions as a coincidence detector for interaural time and phase differences by integrating excitatory synaptic inputs. Recent studies demonstrating glycinergic projections to MSO neurons suggest that coincidence detection results from the temporal integration of both EPSPs and IPSPs. We examined the impact of synaptic inhibition on the temporal coding properties of gerbil MSO neurons in vitro with intracellular recordings and electrical stimulation. For low-level bilateral electric stimulation, the EPSPs summated to produce an action potential in 73% of MSO neurons if they occurred within 50–500 microseconds of one another. Synaptic inhibition became more prominent at higher stimulus amplitudes in 73% of MSO neurons, and could block an evoked action potential if the stimuli to each pathway were delivered within 250 microseconds of one another. The glycine receptor antagonist strychnine influenced the response to simulated interaural time differences. In the presence of strychnine, interstimulus delays that originally resulted in full action potential suppression were sufficient to evoke an action potential. For trains of stimuli, as stimulus intensity increased (spatial summation), or as stimulus repetition rate increased to 100–500 Hz (temporal summation), there was a decrease in the number of stimulus pulses that evoked an action potential. In the presence of strychnine, MSO neurons generated a greater percentage of action potentials to the stimulus trains. When stimulus trains were delivered bilaterally, MSO neurons fired a greater number of action potentials at specific interstimulus time differences, and were selectively inhibited at other time differences.(ABSTRACT TRUNCATED AT 250 WORDS)

A model of dendritic spine Ca2+ concentration exploring possible bases for a sliding synaptic modification threshold

Abstract: We used a biophysical model of an isolated dendritic spine to assess quantitatively the impact of changes in spine geometry, Ca2+ buffer concentration, and channel kinetics on Ca2+ dynamics following high-frequency activation of N-methyl-D-aspartate receptors. We found that varying the buffer concentration in the postsynaptic density from 50 to 500 microM can result in an 8-fold difference in the peak Ca2+ concentration following three pulses at 100 Hz. Similarly, varying the spine neck diameter from 0.1 to 0.55 micron can result in a 15-fold difference in the peak Ca2+ concentration. The amplification of peak Ca2+ concentration also depended on temporal summation of N-methyl-D-aspartate-mediated excitatory postsynaptic currents. Variation of the current duration on the order of 100 msec can significantly affect summation at a given stimulation frequency, resulting in a 10-fold difference in the peak Ca2+ concentration at 100 Hz. It is suggested that activity-dependent modifications of these parameters may be important for the regulation of synaptic plasticity in the brain.

Hippocampal inhibitory neuron activity in the elevated potassium model of epilepsy

Abstract: 1. Whole cell patch-clamp recordings were made from CA1 stratum oriens inhibitory neurons of rat hippocampal slices in vitro to determine their contribution to the epileptiform activity elicited by elevating the extracellular potassium ion concentration ([K+]o) from 3.5 to 8.5 mM. 2. Under current-clamp conditions, spontaneous action potential activity in inhibitory neurons normally occurs in a sustained repetitive firing mode paced by nonsynaptic, intrinsic mechanisms. On elevation of [K+]o to 8.5 mM the pattern of activity is altered such that clusters of action potentials occur interrupted by periods of silence without an appreciable after hyperpolarization (AHP). In addition, elevation of [K+]o caused a large reduction in the action potential AHP amplitude and duration concomitant with a 20-mV shift in the reversal potential of the AHP. 3. In voltage clamp a small persistent inward current was observed after the introduction of elevated potassium concomitant with an increase in the frequency of spontaneous excitatory post-synaptic currents (EPSCs) in all interneurons studied. After a short period of time (approximately 1 min) temporal summation of synchronously occurring EPSCs contributed a periodic inward current (PIC; 10-40 pA, 0.8 Hz) that persisted for the duration of the [K+]o elevation. Analysis of the charge transfer associated with the PIC suggests that they comprise the temporal summation of approximately 35 EPSCs. This PIC was synchronous with the extracellular field potential recorded from the CA1 pyramidal neuron layer. 4. The PIC was responsible for the clustering of action potential activity because blockade of EPSC activity by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) abolished PICs and reverted action potential activity to single sustained firing, despite the continued application of 8.5 mM [K+]o. Antagonists of N-methyl-D-aspartate receptors were without effect on either the PICs or the action potential activity. 5. Addition of the metabotropic glutamate receptor (mGluR) antagonist (+)-2-methyl-4-carboxyphenylglycine (MCPG) reversibly abolished the PIC without affecting the increase in EPSC frequency. 6. Recordings from CA3 pyramidal neurons in 8.5 mM [K+]o demonstrated that interictal activity occurred at a frequency identical to the PICs observed in interneurons. Interictal activity in CA3 pyramidal neurons was attenuated but never abolished by MCPG, suggesting a role for mGluR receptors in the maintenance of interictal activity in area CA3.(ABSTRACT TRUNCATED AT 400 WORDS)

Spatial and temporal response properties of residual vision in a case of hemianopia

Abstract: Residual vision in subjects with damage of the primary visual cortex (striate cortex) has been demonstrated in many previous studies and is taken to reflect the properties of known subcortical and extrastriate visual pathways. In this report we describe psychophysical experiments carried out on a subject clinically blind in half of his visual field (i.e. homonymous hemianopia) caused by striate cortex damage. They reveal the existence of two distinct channels mediating such vision. One channel responds to spatial structure and the other to light flux changes. The spatially tuned channel has a peak response at about 1.2 cycles per degree and shows rapid loss of sensitivity at both high and low spatial frequencies. This channel does not respond to diffuse illumination. The light flux channel, however, responds only to sudden increments in light flux levels on the retina and shows extensive spatial summation. Both channels require transient inputs, with a peak sensitivity at about 10 cycles per second and show virtually complete attenuation at temporal frequencies below 2 cycles per second. The spatiotemporal characteristics of these two channels account for much of the reported limits of visual performance attributed to subcortical or extrastriate pathways in some patients, and especially for their relatively good sensitivity for the detection of abrupt, transient stimuli or fast-moving targets. A new method is also applied to the measurement of the amount of light scatter in the eye. The measurements show that light scatter into the sighted hemifield could not account for the results obtained with the stimuli used to characterized the residual vision of this subject.

The Effects of Aging on Information-Processing Channels in the Sense of Touch: II. Temporal Summation in the P Channel

Abstract: Thresholds for detecting 250-Hz vibrotactile signals of variable duration applied to the thenar eminence of the hand were measured in 16 subjects ranging in age from 19 to 81 years. Detection thresholds were higher in older than in younger subjects. Correlation coefficients for the relation between threshold and age ranged from 0.94 to 0.96, depending on signal duration. In addition, the amount of temporal summation was negatively correlated with age. Both the elevated detection thresholds and the reduced amount of temporal summation in elderly subjects may be partially due to the decrease in the number of Pacinian corpuscles in the hand that occurs with aging. Another factor that could be responsible for reduced temporal summation in older as compared to younger subjects is impairment of the temporal integrator.

The effects of masking on vibrotactile temporal summation in the detection of sinusoidal and noise signals

Abstract: Thresholds for the detection of vibrotactile signals of varied duration applied to the thenar eminence were measured in the absence of and in the presence of a masking stimulus. Signals were 250‐ and 500‐Hz sinusoids and noise bursts with bandwidth limited to 250–1000 Hz. The masking stimulus was either a 250‐Hz sinusoid, which was presented in phase with the signal when it was sinusoidal, or noise. Changes in threshold as a function of changes in signal duration were found which were predicted accurately from Zwislocki’s theory [J. Acoust. Soc. Am. 32, 1046–1060 (1960)] of temporal summation when the signal was detected by the Pacinian channel, but not when it was detected by a non‐Pacinian channel (NP). However, when either the signal or the masking stimulus or both were noise, NP thresholds were affected by changes in signal duration. Only when the signal and masking stimuli were both sinusoids were NP thresholds independent of signal duration. It is concluded that signal duration effects in the NP channel are not due to temporal integration, but rather to increases in information about the signal content provided to the subject as exposure duration is increased.

Linearity and Non‐Linearity in Cortical Receptive Fields

Abstract: Visual neurons in striate (V1) cortex have been studied as feature detectors or as spatiotemporal filters. A useful way to distinguish between these two conceptual approaches is by studying the way in which visual signals are pooled across space and time. Many neurons in layer IV of striate cortex exhibit linear spatial summation and their response time course is consistent with linear temporal summation. Neurons in supragranular and infragranular layers sum signals in a non-linear manner. A particularly important non-linearity seen in many cortical complex cells is non-linear summation along an axis parallel to their preferred orientation. This leads to responsiveness to 'illusory contours', borders defined by texture differences only. These and other results on non-linear summation of chromatic and achromatic signals imply that V1 cortex performs sophisticated and complex image processing and is not simply an array of spatiotemporal filters.

The Influence of Spatial Summation on Human Tactile Directional Sensibility

Abstract: Spatial summation is known to influence the magnitude of sensation for stationary cutaneous stimuli. Yet analysis of moving stimuli may also be pertinent, since most stimuli that attract our attention involve movements over the skin surface. The present investigation dealt with the importance of spatial summation for the appreciation of the direction of motion for moving stimuli. The ability to detect the direction of motion was tested on the radial surface of the forearm with the two-alternative forced-choice method. Stimulation was performed with a rolling wheel, in order to exclude friction-generated activation of stretch receptors. Each subject was tested with two wheels with the same radius but different widths, 1 mm and 15 mm. On average, the subjects performed better with the wide wheel than with the narrow one for stimulation distances > or = 16 mm. This value also probably exceeds the threshold distance for directional discrimination for the narrow wheel, which indicates that spatial summation improves suprathreshold performance.

Modeling of neuronal functions: a neuron-like element with the graded response

Abstract: The JASTAP computer model simulates functional features of a real neuron with chemical transmission of information; it is focused on the simulation of the selected integrative neuronal functions directly influencing the animation of a neuronal network : a) Type and time-course of the synaptic potential (excitatory, excitatory with afterpotential, inhibitory). b) Latency, threshold, absolute refractory period, phasic and tonic spiking activity, synaptic weight, input-output function. c) Spatial and temporal summation. d) Heterosynaptic interactions of the synapses at the presynaptic site (facilitation, inhibition). e) Activity induced changes of the synaptic transmission (habituation, sensitization, fatigue, frequency potentiation, posttetanic depression, posttetanic potentiation, Hebbian learning). This program is written in C++ language for IBM PC compatible computers with 640 kB RAM, VGA graphics card and hard disk (mathematical coprocessor is not required but can significantly speed up computation). The program can define neural network by simple command language and simulate its activity in discrete time intervals on 0.5 ms steps. The results can be displayed in time slices (visualization in the form of the intracellular recording with a microelectrode) or saved to disk files. Ambition of the JASTAP model is to simulate some of the biologically realistic functions of the neuronal networks assembled of several dozens of model neurons

Modelling of the high firing variability of real cortical neurons with the temporal noisy-leaky integrator neuron model

Abstract: Using the temporal noisy-leaky integrator (TNLI) neuron model with reset, we observed that high firing variability can be achieved for certain input parameter values which results from the temporal summation of noise in the dendrites and the use of random synaptic inputs (0-pRAMs). This was done by calculating the rate-normalised coefficient of variation (C/sub v/) of the interspike interval distribution. Recent experimental observations have shown that firing in real cortical neurons is consistent with a near-random process (e.g. C/sub v/=1), but there has been concern that neuron models which use temporal integration of random excitatory postsynaptic potentials (EPSPs) can only produce very low firing variability (C/sub v/ 1) can indeed be achieved, which results from the use of random synapses (0-pRAMs) and distal inputs. For non-bursting behaviour, the irregularity of the output firing of the TNLI increases when inhibitory inputs are added. >

Temporal summation measurements with the Octopus 1-2-3 perimeter.

Abstract: Until recently, measurements of temporal summation required the construction of specialized instrumentation or the custom modification of an existing perimeter, which meant that such testing was unstandardized and relatively expensive. This precluded extensive use of this type of visual response testing, especially in a clinical setting. In an effort to change this situation, a personal computer (PC) program has been devised that makes use of a new interface for remote operation of the Octopus 1-2-3 automated perimeter. The program can be used to measure temporal summation at 1-5 locations in the visual field (0 degrees-30 degrees eccentricity) for 1-10 stimulus durations (5.6-999 ms) in the presence or absence of background illumination (10 cd/m2). Two auxiliary programs for analyzing the resulting data have been developed as well. Preliminary measurement trials were performed on four normal and two glaucomatous eyes at three test locations for ten stimulus durations in both the presence and the absence of background illumination. Ten examinations were carried out for each eye to reduce the effects of short-term fluctuations. The resulting temporal summation curves and the associated critical durations were similar to those found in the literature. No effect of disease on the critical duration was found (n = 2). With this program package, the effects of disease on temporal summation can now be tested using a commercially available instrument. To determine its clinical usefulness, though, investigations with larger populations will have to be made.

Mono- and polysynaptic connections between identified neurons in the system of the passive avoidance reflex of the snail.

Abstract: The structure of the synaptic connections between identified sensory and giant command neurons of the parietal ganglia of the snail is examined. It is shown that the excitatory postsynaptic potential arising in the giant neuron in response to the generation of a single action potential in the presynaptic neuron consists of several monosynaptic components and may include polysynaptic components. It is hypothesized that monosynaptic components of the elementary excitatory postsynaptic potential that differ in the duration of the latent period and the dynamics of habituation may be associated with the activation of synaptic buttons on axon terminals of varying length.

Dynamic Changes in Dorsal Horn Neurons

Abstract: The responses of dorsal horn neurons to somatosensory stimulation can be altered under a variety of circumstances. For example, somatosensory responses of spinal cord dorsal horn neurons can be decreased by 1) habituation following repeated stimulation of the excitatory receptive field;46 2) stimulation of an inhibitory receptive field;30 3) activity in descending inhibitory pathways81 and 4) pathological changes leading to loss of primary afferent fibers.13 Conversely, somatosensory responses can be increased by such manipulations as 1) repeated stimulation of fine calibre primary afferent fibers (“wind-up”);47 2) spatial summation of excitatory inputs from different parts of the receptive field;49 3) volleys in excitatory pathways descending from the brain;80 and 4) sensitization of primary afferent fibers37 or of dorsal horn neurons as a consequence of damage to peripheral tissue or peripheral nerves.19,57

Effects of signal duration on vibrotactile intensity discrimination

Abstract: Vibrotactile intensity DLs were measured by the continuous pedestal and gated pedestal methods. In both cases, the relative DL decreased as a function of the sensation level of the stimulus and the results, in most cases, could be described as a near miss to Weber’s law. DLs measured by the continuous pedestal method were found to decrease substantially as a function of increases in stimulus duration over a range of 12 to 1000 ms and the results could be described by a temporal summation function derived from Zwislocki’s theory of temporal summation [J. J. Zwislocki, J. Acoust. Soc. Am. 32, 1046–1060 (1960)]. In contrast, DLs measured by the gated pedestal method were only slightly affected by changes in stimulus duration. These findings are consistent with the hypothesis that, at suprathreshold levels of stimulation, the effects of temporal summation tend to be cancelled by the effects of adaptation.

Central and Peripheral Aspects of Spatial Summation and Mixture Suppression in Taste

Abstract: Peripheral and central spatial summation and mixture suppression in taste were investigated by the “split-tongue” technique. In this method, stimuli are applied to one or both sides of the tongue in different combinations. Interactions between tongue sides must be central, whereas comparison with unilateral results provides information about peripheral vs central contributions [1].