Showing papers on "Summation published in 2000"
TL;DR: This review discusses how passive and active dendritic properties, and the functional characteristics of the synapse, shape these three elements of synaptic integration.
Abstract: A fundamental function of nerve cells is the transformation of incoming synaptic information into specific patterns of action potential output. An important component of this transformation is synaptic integration--the combination of voltage deflections produced by a myriad of synaptic inputs into a singular change in membrane potential. There are three basic elements involved in integration: the amplitude of the unitary postsynaptic potential; the manner in which non-simultaneous unitary events add in time (temporal summation), and the addition of unitary events occurring simultaneously in separate regions of the dendritic arbor (spatial summation). This review discusses how passive and active dendritic properties, and the functional characteristics of the synapse, shape these three elements of synaptic integration.
668 citations
TL;DR: The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA‐antagonist in FMS patients, and suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summary in a sub‐group of the fibromyalgia syndrome patients.
Abstract: Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the ef ...
380 citations
TL;DR: Data indicate that an increasing density of apical dendritic I(h) channels mitigates the influence of cable filtering on somatic EPSP time course and temporal summation in neocortical layer 5 pyramidal neurons.
Abstract: Neocortical layer 5 pyramidal neurons possess long apical dendrites that receive a significant portion of the neurons excitatory synaptic input. Passive neuronal models indicate that the time course of excitatory postsynaptic potentials (EPSPs) generated in the apical dendrite will be prolonged as they propagate toward the soma. EPSP propagation may, however, be influenced by the recruitment of dendritic voltage-activated channels. Here we investigate the properties and distribution of I(h) channels in the axon, soma, and apical dendrites of neocortical layer 5 pyramidal neurons, and their effect on EPSP time course. We find a linear increase (9 pA/100 microm) in the density of dendritic I(h) channels with distance from soma. This nonuniform distribution of I(h) channels generates site independence of EPSP time course, such that the half-width at the soma of distally generated EPSPs (up to 435 microm from soma) was similar to somatically generated EPSPs. As a corollary, a normalization of temporal summation of EPSPs was observed. The site independence of somatic EPSP time course was found to collapse after pharmacological blockade of I(h) channels, revealing pronounced temporal summation of distally generated EPSPs, which could be further enhanced by TTX-sensitive sodium channels. These data indicate that an increasing density of apical dendritic I(h) channels mitigates the influence of cable filtering on somatic EPSP time course and temporal summation in neocortical layer 5 pyramidal neurons.
355 citations
TL;DR: The results of clinical trials in patients with chronic pain suggest that the NMDA receptor may represent a new target for modulation of abnormal temporal summation of pain, as well as other characteristics of chronic pain.
293 citations
TL;DR: The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A‐type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and theaction potentials occur within the appropriate time window.
Abstract: Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 micrometer of the apical dendrites, so that action potentials recorded farther than 200 micrometer from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials.
265 citations
TL;DR: The wind-up phenomenon was characterized in humans by using electrophysiological recordings of the nociceptive flexion reflex and it was showed that this phenomenon, which might represent an elementary form of the central sensitization involved in various painful syndromes, depends on the activation of N-methyl-D-aspartate receptors, because it was selectively reduced after the administration of ketamine.
Abstract: UNLABELLED Animal studies have suggested that the temporal summation of nociceptive inputs might play a significant role in the development of central sensitization (i.e., hyperexcitability of central nociceptive neurons) and hyperalgesia via the activation of N-methyl-D-aspartate receptors. To further analyze these processes in humans, we evaluated the effects of small systemic doses of ketamine on the temporal summation (i.e., wind-up) of both the nociceptive flexion (R(III)) reflex and sensations of pain in six healthy volunteers. The R(III) reflex was recorded from the biceps femoris and was elicited by electrical stimulation of the sural nerve. First, the recruitment (stimulus/response) curve for the reflex was built using stimuli up to the pain tolerance threshold (applied once every 6 s). A series of 15 stimuli was then applied once a second at an intensity of 1.2 times the reflex threshold. These procedures were performed both before and after the randomized IV injection of either 0.15 mg/kg ketamine or a placebo. The R(III) reflex threshold and its recruitment curve were not significantly altered after the injection of ketamine or placebo. By contrast, the significant increases (i.e., wind-up) in both the reflex responses and the sensations of pain observed during the higher frequency stimulation were significantly reduced after the administration of ketamine, but not placebo. This method might be useful for quantifying and analyzing the wind-up phenomenon and, thus, for studying the neurophysiological and pharmacological mechanisms underlying hyperalgesia in humans. IMPLICATIONS The wind-up phenomenon (i.e., the progressive increase of the responses induced by repetitive nociceptive stimuli) was characterized in humans by using electrophysiological recordings of the nociceptive flexion reflex. We showed that, as in animals, this phenomenon, which might represent an elementary form of the central sensitization involved in various painful syndromes, depends on the activation of N-methyl-D-aspartate receptors, because it was selectively reduced after the administration of ketamine.
152 citations
TL;DR: It is demonstrated clearly that a stimulus that is perceived as a localised, repetitive tactile tap can be integrated and cause severe pain, and suggests that pathologically generated sparse nociceptive afferent activity causes strong pain by central integration.
Abstract: In the present human study, we aimed to investigate the facilitation of both the subjective pain responses, and the withdrawal reflex to consecutive transcutaneous electrical stimuli as measures of temporal summation. The frequency (0.5-20 Hz) and intensity (0.4-0.8 times the reflex threshold, xRT) of the electrical stimuli were systematically varied. When using repeated stimulation, the stimulus intensity that evoked pain was lower than that required by a single stimulus (temporal summation). Temporal summation leading to pain was found to depend significantly upon both frequency and intensity (e.g. stimulation at 1 Hz caused summation at 0.8 x RT, whereas stimulation at 20 Hz caused summation at 0.6 x RT). The strongest reflex facilitation, and hence the strongest pain intensity was obtained for stimulation at 10-20 Hz at an intensity of 0.8 x RT. In conclusion, the results of the present human study demonstrate clearly that a stimulus that is perceived as a localised, repetitive tactile tap can be integrated and cause severe pain. This suggests that pathologically generated sparse nociceptive afferent activity causes strong pain by central integration. This might be one mechanism to explain why clinical conditions can become excruciatingly painful despite the fact that the pathophysiological changes seem to be marginal (e.g. minor nerve trauma).
130 citations
TL;DR: It is concluded that amplification of backpropagating action potentials during physiological spike trains is mediated by frequency-dependent supralinear temporal summation, generated by the recruitment of distal dendritic sodium and calcium channels.
Abstract: In vivo neocortical neurons fire apparently random trains of action potentials in response to sensory stimuli. Does this randomness represent a signal or noise around a mean firing rate? Here we use the timing of action potential trains recorded in vivo to explore the dendritic consequences of physiological patterns of action potential firing in neocortical pyramidal neurons in vitro . We find that action potentials evoked by physiological patterns of firing backpropagate threefold to fourfold more effectively into the distal apical dendrites (>600 μm from the soma) than action potential trains reflecting their mean firing rate. This amplification of backpropagation was maximal during high-frequency components of physiological spike trains (80–300 Hz). The disparity between backpropagation during physiological and mean firing patterns was dramatically reduced by dendritic hyperpolarization. Consistent with this voltage dependence, dendritic depolarization amplified single action potentials by fourfold to sevenfold, with a spatial profile strikingly similar to the amplification of physiological spike trains. Local blockade of distal dendritic sodium channels substantially reduced amplification of physiological spike trains, but did not significantly alter action potential trains reflecting their mean firing rate. Dendritic electrogenesis during physiological spike trains was also reduced by the blockade of calcium channels. We conclude that amplification of backpropagating action potentials during physiological spike trains is mediated by frequency-dependent supralinear temporal summation, generated by the recruitment of distal dendritic sodium and calcium channels. Together these data indicate that the temporal nature of physiological patterns of action potential firing contains a signal that is transmitted effectively throughout the dendritic tree.
97 citations
TL;DR: The data suggest that the strongest input to cortical cells will arise from geniculate cells representing areas of visual space located at the borders of a visual stimulus, and suggests that analysis of response properties by patterns centred over the receptive fields of cells may give a misleading impression of the process of the representation.
Abstract: We have compared the spatial summation characteristics of cells in the primary visual cortex with those of cells in the dorsal lateral geniculate nucleus (LGN) that provide the input to the cortex. We explored the influence of varying the diameter of a patch of grating centred over the receptive field and quantitatively determined the optimal summation diameter and the degree of surround suppression for cells at both levels of the visual system using the same stimulus parameters. The mean optimal summation size for LGN cells (0.90°) was much smaller than that of cortical cells (3.58°). Virtually all LGN cells exhibited strong surround suppression with a mean value of 74%±1.61% SEM for the population as a whole. This potent surround suppression in the cells providing the input to the cortex suggests that cortical cells must integrate their much larger summation fields from the low firing rates associated with the suppression plateau of the LGN cell responses. Our data suggest that the strongest input to cortical cells will arise from geniculate cells representing areas of visual space located at the borders of a visual stimulus. We suggest that analysis of response properties by patterns centred over the receptive fields of cells may give a misleading impression of the process of the representation. Analysis of pattern terminations or salient borders over the receptive field may provide much more insight into the processing algorithms involved in stimulus representation.
94 citations
TL;DR: The results strongly suggest that giant depolarizing potentials are locally generated from different initiation sites and not from a single region, in view of the principles underlying hyperexcitability in hippocampal slices, i.e. the intrinsic firing properties of individual cells and the connectivity patterns.
50 citations
TL;DR: Nonlinear spatial summation is consistent with probabilistic summation across independent detecting mechanisms that vary in spatial frequency, orientation and position and in further experiments, results were found to be consistent with probability summation for pairs of orthogonally oriented step-edge stimuli and a matrix of randomly oriented 11 c/deg sine-wave patches.
TL;DR: The maximum area of complete spatial summation (i.e., Ricco's area) for human short-wavelength-sensitive- (S-) and longwavelength sensitive- (L-) cone mechanisms was measured psychophysically at the fovea and at 1.5°, 4°, 8°, and 20° along the vertical meridian in the superior retina as mentioned in this paper.
Abstract: The maximum area of complete spatial summation (i.e., Ricco’s area) for human short-wavelength-sensitive- (S-) and long-wavelength-sensitive- (L-) cone mechanisms was measured psychophysically at the fovea and at 1.5°, 4°, 8°, and 20° along the vertical meridian in the superior retina. Increment thresholds were measured for three observers by a temporal two-alternative forced-choice procedure. Test stimuli ranging from -0.36 to 4.61 log area (min2) were presented on concentric 12.3° adapting and auxiliary fields, which isolated either an S- or an L-cone mechanism on the plateau of its respective threshold versus intensity function. Test flash durations were 50 and 10 ms for the S- and L-cone mechanisms, respectively. The data indicate that, from 0° to 20°, Ricco’s area increases monotonically for the L-cone mechanism, is variable for the S-cone mechanism, and is larger for the S-cone mechanism than for the L-cone mechanism for essentially all retinal locations. This pattern of results most likely reflects differences in ganglion cell density and changes in neural convergence with retinal eccentricity.
TL;DR: A simple model for the spatial receptive-field organization of nonlagged X-cells is presented, that is consistent with the findings, and suggests that both excitatory and inhibitory transmission in dLGN are close to linear.
Abstract: Spatial summation and degree of center-surround antagonism were examined in the receptive field of nonlagged cells in the dorsal lateral geniculate nucleus (dLGN). We recorded responses to stationary light or dark circular spots that were stepwise varied in width. The spots were centered on the receptive field. For a sample of nonlagged X-cells, we made simultaneous recordings of action potentials and S-potentials, and could thereby compare spatial summation in the dLGN cell and in the retinal input to the cell. Plots of response versus spot diameter showed that the response for a dLGN cell was consistently below the response in the retinal input at all spot sizes. There was a marked increase of antagonism at the retinogeniculate relay. The difference between the retinal input and dLGN cell response suggested that the direct retinal input to a relay cell is counteracted in dLGN by an inhibitory field that has an antagonistic center-surround organization. The inhibitory field seems to have the same center sign (ON- or OFF-center), but a wider receptive-field center than the direct retinal input to the relay cell. The broader center of the inhibitory field can explain the increased center-surround antagonism at the retinogeniculate relay. The ratio between the response of a dLGN cell and its retinal input (transfer ratio) varied with spot width. This variation did not necessarily reflect a nonlinearity at the retinogeniculate relay. Plots of dLGN cell response against retinal input were piecewise linear, suggesting that both excitatory and inhibitory transmission in dLGN are close to linear. The variation in transfer ratio could be explained by sustained suppression evoked by the background stimulation, because such suppression has relatively stronger effect on the response to a spot evoking weak response than to a spot evoking a strong response. A simple model for the spatial receptive-field organization of nonlagged X-cells, that is consistent with our findings, is presented.
TL;DR: The presence of muscle hyperalgesia and central hyper-excitability in postexercise muscle soreness was induced by standardized eccentric exercise of the first dorsal interosseous muscle of the right hand using a newly designed hand exerciser and the ultrasonic stimuli were used to assess the FDI.
TL;DR: The simulations described in this paper provide insights into mechanisms of axonal excitation that can be carried out by following an easily understood protocol.
TL;DR: Experiments with red-on-red stimuli confirmed that the large summation area and stimulus-polarity-dependent spatial summation are specific for the isolated S-cone signals.
TL;DR: Two neural network models based on possible effects of synchronization and sensitivity enhancement caused by inhibitory inputs to neurons with a biologically realistic model of the Hodgkin-Huxley equations are proposed to demonstrate possible mechanisms of detecting particular spatiotemporal spike patterns.
Abstract: Recent experimental results imply that inhibitory postsynaptic potentials can play a functional role in realizing synchronization of neuronal firing in the brain. In order to examine the relation between inhibition and synchronous firing of neurons theoretically, we analyze possible effects of synchronization and sensitivity enhancement caused by inhibitory inputs to neurons with a biologically realistic model of the Hodgkin-Huxley equations. The result shows that, after an inhibitory spike, the firing probability of a single postsynaptic neuron exposed to random excitatory background activity oscillates with time. The oscillation of the firing probability can be related to synchronous firing of neurons receiving an inhibitory spike simultaneously. Further, we show that when an inhibitory spike input precedes an excitatory spike input, the presence of such preceding inhibition raises the firing probability peak of the neuron after the excitatory input. The result indicates that an inhibitory spike input can enhance the sensitivity of the postsynaptic neuron to the following excitatory spike input. Two neural network models based on these effects on postsynaptic neurons caused by inhibitory inputs are proposed to demonstrate possible mechanisms of detecting particular spatiotemporal spike patterns.
TL;DR: A clear temporal summation of psychophysical ratings, reduction of the peak amplitudes in the last of the first stimuli, dissociation from simple amplitude increase of the cerebral responses to pain, and a concurrent transformation of the CSD patterns are demonstrated.
Abstract: Temporal summation is a potent central somatosensory mechanism and may be a major mechanism involved in e.g. neuropathic pain. This study assessed the long-latency somatosensory evoked potentials (SEPs) in response to trains of repeated painful electrical stimulation of human skin and muscle in order to investigate the cerebral representation of temporal summation. Forty series of stimuli were delivered at stimulus intensities corresponding to moderate pain levels in 20 young men. Each series consisted of a five-burst-pulses (1 ms) train delivered at 2 Hz, known to activate temporal summation, i.e. increased pain intensity during the series of stimuli. Grand mean averaged waveforms (31 ch. EEG) were obtained in response to the skin and muscle stimulation. In the "train" SEPs, the wave morphology was characterized by four peak components after the first stimulus (100 to 450 ms) and by three components after the fifth stimulus (2100-2145 ms). The latency was significantly prolonged for muscle stimulation only. The 3D topographic maps at the peak activation time (100, 140, 250, and 450 ms) showed clear reduction in the amplitudes and their spatial extent (P4/P100-Fc2/N100, POz/P140-Fc2/N140, Cz/P250, Cz/N460) betweenthe first and the fifth stimulus. The current source density (CSD) topology exhibited markedly differential patterns changing from the first to the fifth stimulus. For the skin stimulation, the fifth stimulus was associated with a distinct emergence of the frontal negativity source at Fc2 right frontal cortex. This was consistent across the 100,140, 250, and 450 peak components but was not even visible in the first stimulus. In the muscle, the fifth stimulus was associated with a marked reduction of the frontal positivity at contralateral F4 site in the early stages at 100 and 140 ms, and with a total disappearance of positive source at Cz. In summary, this study demonstrated a clear temporal summation of psychophysical ratings, reduction of the peak amplitudes in the last of the first stimuli, dissociation from simple amplitude increase of the cerebral responses to pain, and a concurrent transformation of the CSD patterns. This change in "rapid cortical dynamics" of short-term plasticity could be an important mechanism for wind-up and pain processing in the brain.
TL;DR: In intact rats, an inhibitory mechanism counteracts the increase in excitability of a flexor reflex, which is seen in spinal animals following temporal summation of C-fibre inputs; the Rostral Ventromedial Medulla is involved in this inhibitory mechanisms.