Showing papers on "Summation published in 1998"

Dendritic Hyperpolarization-Activated Currents Modify the Integrative Properties of Hippocampal CA1 Pyramidal Neurons

Abstract: Step hyperpolarizations evoked slowly activating, noninactivating, and slowly deactivating inward currents from membrane patches recorded in the cell-attached patch configuration from the soma and apical dendrites of hippocampal CA1 pyramidal neurons. The density of these hyperpolarization-activated currents (Ih) increased over sixfold from soma to distal dendrites. Activation curves demonstrate that a significant fraction of Ih channels is active near rest and that the range is hyperpolarized relatively more in the distal dendrites. Ih activation and deactivation kinetics are voltage-and temperature-dependent, with time constants of activation and deactivation decreasing with hyperpolarization and depolarization, respectively. Ih demonstrated a mixed Na+-K+ conductance and was sensitive to low concentrations of external CsCl. Dual whole-cell recordings revealed regional differences in input resistance (Rin) and membrane polarization rates (taumem) across the somatodendritic axis that are attributable to the spatial gradient of Ih channels. As a result of these membrane effects the propagation of subthreshold voltage transients is directionally specific. The elevated dendritic Ih density decreases EPSP amplitude and duration and reduces the time window over which temporal summation takes place. The backpropagation of action potentials into the dendritic arborization was impacted only slightly by dendritic Ih, with the most consistent effect being a decrease in dendritic action potential duration and an increase in afterhyperpolarization. Overall, Ih acts to dampen dendritic excitability, but its largest impact is on the subthreshold range of membrane potentials where the integration of inhibitory and excitatory synaptic inputs takes place.

Synaptic Depression and the Temporal Response Characteristics of V1 Cells

Abstract: We explore the effects of short-term synaptic depression on the temporal dynamics of V1 responses to visual images by constructing a model simple cell. Synaptic depression is modeled on the basis of previous detailed fits to experimental data. A component of synaptic depression operating in the range of hundreds of milliseconds can account for a number of the unique temporal characteristics of cortical neurons, including the bandpass nature of frequency‐response curves, increases in response amplitude and in cutoff frequency for transient stimuli, nonlinear temporal summation, and contrastdependent shifts in response phase. Synaptic depression also provides a mechanism for generating the temporal phase shifts needed to produce direction selectivity, and a model constructed along these lines matches both extracellular and intracellular data. A slower component of depression can reproduce the effects of contrast adaptation.

Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagating action potentials and subthreshold excitatory postsynaptic potentials

Abstract: We compared the transient increase of Ca2+ in single spines on basal dendrites of rat neocortical layer 5 pyramidal neurons evoked by subthreshold excitatory postsynaptic potentials (EPSPs) and back-propagating action potentials (APs) by using calcium fluorescence imaging. AP-evoked Ca2+ transients were detected in both the spines and in the adjacent dendritic shaft, whereas Ca2+ transients evoked by single EPSPs were largely restricted to a single active spine head. Calcium transients elicited in the active spines by a single AP or EPSP, in spines up to 80 μm for the soma, were of comparable amplitude. The Ca2+ transient in an active spine evoked by pairing an EPSP and a back-propagating AP separated by a time interval of 50 ms was larger if the AP followed the EPSP than if it preceded it. This difference reflected supra- and sublinear summation of Ca2+ transients, respectively. A comparable dependence of spinous Ca2+ transients on relative timing was observed also when short bursts of APs and EPSPs were paired. These results indicate that the amplitude of the spinous Ca2+ transients during coincident pre- and postsynaptic activity depended critically on the relative order of subthreshold EPSPs and back-propagating APs. Thus, in neocortical neurons the amplitude of spinous Ca2+ transients could encode small time differences between pre- and postsynaptic activity.

Sex differences in temporal summation but not sensory-discriminative processing of thermal pain

Abstract: Gender differences in experimental pain sensitivity have been widely investigated, and the results generally indicate that females exhibit greater sensitivity to noxious stimuli than males. However, results using thermal pain procedures have been inconsistent, with some studies reporting greater responses among females and other studies reporting no gender differences. The present study investigated gender differences in thermal pain perception using several different psychophysical procedures. Twenty-seven females and 22 males underwent thermal testing, including: determination of thermal pain threshold and tolerance, a thermal discrimination procedure, real-time magnitude estimates of heat pulses, and temporal summation of thermal pain. The results indicated lower thermal pain threshold and tolerance and greater temporal summation of thermal pain among females, but no gender differences in thermal discrimination or real-time magnitude estimates of discrete heat pulses. These findings suggest that gender differences in thermal pain perception may be more robust for sustained, temporally dynamic thermal stimuli with a strong C-fiber component.

Temporal integration can readily switch between sublinear and supralinear summation

Abstract: Margulis, Michael and Cha-Min Tang. Temporal integration can readily switch between sublinear and supralinear summation. J. Neurophysiol. 79: 2809–2813, 1998. Temporal summation at dendrites of cul...

The relationship between sensory thresholds and mechanical hyperalgesia in nerve injury.

Abstract: The paradoxical combination of sensory loss within the area where pain is felt together with pain evoked by non-noxious stimuli (allodynia) is a characteristic feature of neuropathic pain. This study examined the relationship between (mechanical and thermal) pain thresholds and dynamic and static hyperalgesia in 15 patients with traumatic nerve injury and brush-evoked pain. Sensory tests were carried out both in the allodynic skin area and in the unaffected contralateral mirror image skin. The sensory characteristics included: visual analogue scale (VAS) score of ongoing pain, detection and pain threshold to thermal and mechanical stimuli, and temporal summation to repetitive heat and pinprick stimuli. Temporal summation was evoked by pinprick stimuli at 2.0 Hz but not at 0.2 Hz in allodynic skin. No difference was observed in temporal summation to heat stimuli. There was a significant and inverse relation between heat and cold pain difference and mechanically evoked pain. Patients with heat hyperalgesia had a significantly higher VAS score of mechanical hyperalgesia than patients with heat hypoalgesia. There was no relationship between dynamic and static evoked hyperalgesia. These findings suggest a differential processing of repetitive thermal and mechanical stimuli in the central nervous system. Both dynamic and static mechanical hyperalgesia are maintained by activity in heat-sensitive nociceptors, but they are probably mediated by distinct mechanisms.

Active summation of excitatory postsynaptic potentials in hippocampal CA3 pyramidal neurons

Abstract: The manner in which the thousands of synaptic inputs received by a pyramidal neuron are summed is critical both to our understanding of the computations that may be performed by single neurons and of the codes used by neurons to transmit information. Recent work on pyramidal cell dendrites has shown that subthreshold synaptic inputs are modulated by voltage-dependent channels, raising the possibility that summation of synaptic responses is influenced by the active properties of dendrites. Here, we use somatic and dendritic whole-cell recordings to show that pyramidal cells in hippocampal area CA3 sum distal and proximal excitatory postsynaptic potentials sublinearly and actively, that the degree of nonlinearity depends on the magnitude and timing of the excitatory postsynaptic potentials, and that blockade of transient potassium channels linearizes summation. Nonlinear summation of synaptic inputs could have important implications for the computations performed by single neurons and also for the role of the mossy fiber and perforant path inputs to hippocampal area CA3.

Hyperalgesia and temporal summation of pain after heat injury in man

Abstract: Temporal summation of pain occurs when repeated stimuli become increasingly painful in spite of unchanged stimulus intensity. Summation can be quantified as the difference in pain between the first and the last stimulus in a train of stimuli. The aim of the study was to compare temporal summation of pain in normal skin with summation of pain in skin with primary and secondary hyperalgesia evoked by a heat injury. A heat injury was produced on the crus of 12 volunteers with a 50×25 mm thermode (47°C, 7 min). Measurements were made before, and 0, 1, 2, and 4 h after the heat injury, in three areas: primary and secondary mechanical hyperalgesia induced by the heat injury, and in a mirror image of the injury on the opposite leg. Temporal summation of pain was induced by repeated electrical stimuli (five stimuli at 2 Hz) and assessed by visual analog scale (VAS). Primary hyperalgesia was evaluated by von Frey hairs and electrical stimuli, and the areas of secondary hyperalgesia with a rigid von Frey hair (314 mN). Significant primary (P<0.000001) and secondary (P<0.00006) mechanical hyperalgesia were evoked by the heat injury. The pain threshold to single electrical stimuli was reduced within the injury (P<0.03), but not outside. The pain responses to single and repeated electrical stimuli were not significantly altered by the injury. Temporal summation of pain occurred in 418 stimulus trains out of 576 (73%), but no significant changes in summation developed in skin with primary or secondary mechanical hyperalgesia compared with normal skin (baseline measurements). Temporal summation at high stimulus intensities was more pronounced than at lower intensities (P<0.0002). We found no correlation between either temporal summation and area of secondary hyperalgesia, or temporal summation and pain intensity during the induction of heat injury. We conclude that the development of primary and secondary mechanical hyperalgesia after heat injury in man was not associated with changes in temporal summation of painful electrical stimuli.

Involvement of the Caudal Medulla in Negative Feedback Mechanisms Triggered by Spatial Summation of Nociceptive Inputs

Abstract: Gall, Olivier, Didier Bouhassira, Djamel Chitour, and Daniel Le Bars. Involvement of the caudal medulla in negative feedback mechanisms triggered by spatial summation of nociceptive inputs. J. Neur...

Recordings of polymodal single C-fiber nociceptive afferents following mechanical and argon-laser heat stimulation of human skin

Abstract: Recordings were made in the peroneal nerve of healthy volunteer subjects from C-mechano-heat (CMH) nociceptors (n=25) with their receptive fields in the skin on the dorsum of the foot. The investigation focused on afferent single C-fiber activity induced by short (200 ms) high-intensity argon-laser light pulses projected to localized spots of the skin. Cutaneous heat stimulation with the argon laser, 2–3 times the activation threshold, induced inter-burst spike frequencies in the nerve, reaching 50 Hz, while mechanical stimulation 10–20 times threshold only evoked frequencies reaching 10 Hz. The decrease in conduction velocity of action potentials in the C-fiber afferents following mechanical and heat stimulation was closely related to the degree of activation. Following a laser pulse of 200 ms, a spike pattern with highly reproducible inter-spike intervals was evoked with a fast saturation. On the contrary, a high variability in the number of action potentials evoked by both heat and mechanical stimuli was found, depending on the location of stimuli within the receptive field. A relation between the conduction velocity and the peak firing within the spike train following laser stimulation was detected. Heat and mechanical stimulation activated single C-fibers in matching spots within the same skin areas, in line with the assumption that the two modalities in the CMH-fibers share matching morphological cutaneous substrates. No correlation was found in thresholds or excitability to mechanical and heat stimulation, respectively. This suggests that subsets of receptors exist within nerve endings of the cutaneous receptive fields, with the ability to generate action potentials independent of heat and mechanical stimuli. Unexpectedly, no signs of sensitization or other inflammatory responses were observed after repeated laser pulses; on the contrary, a rapidly developing fatigue was observed when single spots were repeatedly stimulated. However, no fatigue was observed if neighboring spots were stimulated, indicating a localized generator of the fatigue. In each subject, a good correlation was observed between the reported pain sensation and the activity evoked in the afferent C-fibers by the laser. However, the magnitude of the reported pain sensation to comparable degrees of C-fiber activation showed a high variability between different subjects. A fairly good subjective estimate of the afferent-fiber activation was observed when skin spots from 3- down to 1-mm diameter were stimulated. In a few individuals, no painful sensation was reported when the stimulated spots were reduced to 1-mm diameter, despite the occurrence of multiple spikes in single C-fiber afferents, amplifying the importance of spatial summation in the perception of pain.

Relief of trigeminal neuralgia after percutaneous retrogasserian glycerol rhizolysis is dependent on normalization of abnormal temporal summation of pain, without general impairment of sensory perception.

Abstract: OBJECTIVE: This study was undertaken to examine the pathophysiological mechanisms of trigeminal neuralgia and the mechanisms underlying pain relief after percutaneous retrogasserian glycerol rhizolysis (PRGR). METHODS: Quantitative examination of sensory and pain perception was performed in the trigger area and the contralateral nonpainful facial skin area for 39 patients with trigeminal neuralgia who had been previously treated with PRGR and for 14 non-surgically treated patients. In a prospective study, 9 of the 14 patients were examined before and 4 to 6 weeks after PRGR. RESULTS: In the trigger area of patients who had been previously treated with PRGR for trigeminal neuralgia, we demonstrated increased temperature and tactile thresholds in pain-free patients and in patients with paroxysmal or continuous pain. Abnormal temporal summation of pain (characterized by progressive increases in pain intensity, with radiation of pain and aftersensation) was present in patients with paroxysmal or continuous pain but not in pain-free patients. In the trigger area of non-surgically treated patients with trigeminal neuralgia, we demonstrated significantly increased temperature and tactile thresholds and the presence of abnormal temporal summation of pain. The prospective study showed that pain relief after PRGR was associated with normalization of abnormal temporal summation of pain, without increased sensory loss. CONCLUSION: Partial deafferentation, with impairment of thin (C/A6) and thick (Aβ) fiber-mediated sensations and abnormal temporal summation of pain, is present in the trigger area of patients with trigeminal neuralgia. Relief of pain after PRGR depends on the normalization of abnormal temporal summation of pain, which is independent of general impairment of sensory perception. Assessment of the temporal summation of pain may serve as an important tool to record central neuronal hyperexcitability, which may play a key role in the pathophysiological changes in trigeminal neuralgia.

Characteristics of anisometropic suppression: Simple reaction time measurements

Abstract: The characteristics of artificially induced anisometropic suppression were investigated in observers with normal and abnormal binocular vision (anisometropic amblyopia) by using a simple reaction time paradigm. Reaction time was measured as a function of stimulus intensity for various stimulus durations. For all conditions, the reaction time increased as stimulus intensity decreased toward threshold. We found that traditional techniques for modeling this trend were inadequate, so we developed a simple visuogram method for comparing these functions. Using this technique, reaction time versus intensity functions are shown to be shape-invariant for all conditions examined. This means that, although reaction times are longer during induced anisometropic suppression or in anisometropic amblyopia, they are the same if contrast is normalized to equate threshold. The shape-invariant nature of these functions is also consistent with the notion that a single mechanism mediates detection under these conditions. Temporal summation was investigated at both threshold (method of limits) and suprathreshold (criterion reaction time) levels. Again, because of shape invariance, the suprathreshold results mirror the threshold results. The critical duration (the duration at the intersection of the complete summation and zero summation regions) is not affected by any of the conditions. However, the critical intensity (the intensity for the zero summation region) is higher for the amblyopic eyes, as compared with the normal or nonamblyopic eyes. Induced anisometropic suppression always increases the critical intensity, with a smaller increase occurring for the amblyopic eyes. This suggests that amblyopic eyes do not have a need for strong suppression.

A possible basic cortical microcircuit called ’’cascaded inhibition’’Results from cortical network models and recording experiments from striate simple cells

Abstract: The robust behavior, the degree of response linearity, and the aspect of contrast gain control in visual cortical simple cells are (amongst others) the result of the interplay between excitatory and inhibitory afferent and intracortical connections. The goal of this study was to suggest a simple intracortical connection pattern, which could also play a role in other cortical substructures, in order to generically obtain these desired effects within large physiological parameter ranges. To this end we explored the degree of linearity of spatial summation in visual simple cells experimentally and in different models based on half-wave rectifying cells (’’push-pull models’’). Visual cortical push-pull connection schemes originated from antagonistic motor-control models. Thus, this model class is widely applicable but normally requires a rather specific design. On the other hand we showed that a more generic version of a push-pull model, the so-called cascaded inhibitory intracortical connection scheme, which we implemented in a biologically realistic simulation, naturally explains much of the experimental data. We investigated the influence of the afferent and intracortical connection structure on the measured linearity of spatial summation in simple cells. The analysis made use of the relative modulation measure, which is easy to apply but is limited to moving sinusoidal grating stimuli. We introduced two basic push-pull models, where the order of threshold nonlinearity and linear summation is reversed. Very little difference is observed with the relative modulation measure for these models. Alterative models, like half-wave squaring models, were also briefly discussed. Of all model parameters, the ratio of excitation to inhibition in the simple cell exerts the most crucial influence on the relative modulation. Linearity deteriorates as soon as excitatory and inhibitory inputs are imbalanced and the relative modulation drops. This prediction was tested experimentally by extracellular recordings from cat area 17 simple cells and we found that about 62% showed a significant deviation from linear behavior. The problem that individual basic push-pull models are hard to distinguish experimentally led us to suggest a different solution. In order to generically account for the observed behavior (e.g., imbalance of excitation versus inhibition), we suggested a rather generic version of a push-pull model where it no longer mattered about (the hard-to-distinguish) fine differences in connectivity. Thus, we introduced a new class of biophysically realistic models (’’cascaded inhibition’’). This model class requires very little connection specificity and is therefore highly robust against parameter variations. Up to 25 cells are connected to each target cell. Thereby a highly interconnected network is generated, which also leads to disinhibition at some parts of an individual receptive field. We showed that the performance of these models simulates the degree of linearity and its variability in recal simple cells with comparatively high accuracy. This behavior can be explained by the self-regulating properties of a cascaded inhibitory connection scheme by which the balance between excitation and inhibition at a given cell is improved by the joint network effects. The virtues and the generic design of this connection pattern, therefore, allow to speculate that it is used also in other parts of the cortex.

Temporal Interactions Between Postsynaptic Potentials

Abstract: The previous two chapters have introduced two of the essential ingredients for the description of neuronal behavior. Chapter 5 has discussed the passive propagation of synaptic inputs through the dendritic tree to the soma and the initial axon segment. Here, voltage-activated channels (Chapter 4) respond to produce the action potentials that are conducted along the axon, resulting in a release of neurotransmitters at the presynaptic terminals. The present chapter deals with the response of the postsynaptic region to this input — namely, with the development of the postsynaptic potential (PSP).

Symmetry and spatial summation properties of the integration field of cat^s striate cortical neurons

Abstract: The extent, strength of inhibition and spatial summation property of sub-regions of the integration fields (IF) of striate cortical neurons were studied using sinusoidal grating patches drifted across the classical receptive field (CRF) and the IF. The results show that (a) the nature of integration (facilitatory or inhibitory) was the same between the two side-regions (and/or the two end-regions) of the IFs; (b) for most neuron, the exteats of the two side-regions (and/or the two end-regions) were equal or roughly equal; (c) for inhibitory IFs, the degree of inhibition at the two side-regions (and/or the two end-regions) was statistically correlative; (d) the spatial summation between the two side-regions (and/or the two end-regions) was shown to be nonlinear.

Cochlear implant threshold changes at high electric stimulus pulse rates

Abstract: Inferior colliculus (IC) units have a significantly lower stimulus threshold when driven with a cochlear implant using bipolar stimuli at high (2 k pulses/s) compared to low (125 pulse/s) pulse rates. At high pulse rates temporal summation is used to explain this threshold shift.

lesions in the rostral ventromedial medulla RVM

Abstract: In intact rats, an inhibitory mechanism counteracts the increase in excitability of a flexor reflex seen in spinal animals following . high-intensity, repetitive stimulation of C-fibres. We tested the hypothesis that the rostral ventromedial medulla RVM is involved in these processes. Electromyographic responses elicited by electrical stimulation of the sural nerve, were recorded from the ipsilateral biceps femoris in halothane-anaesthetised, sham-operated or RVM-lesioned rats. There were no significant differences between the C-fibre reflexes in the two groups in terms of their thresholds, latencies, durations or mean recruitment curves. The excitability of the C-fibre reflex was tested following 20 s of high-intensity homotopic electrical conditioning stimuli at 1 Hz. During the conditioning . period, the EMG responses first increased in both groups the wind-up phenomenon , but then decreased in the sham-operated rats and plateaued in the RVM-lesioned rats. These effects were followed by inhibitions that were very much smaller in the RVM-lesioned rats, both in terms of their magnitudes and their durations. It is concluded that the RVM is involved in inhibitory feedback mechanisms elicited by temporal summation of C-fibre afferents that both counteract the wind-up phenomenon and trigger long periods of inhibition. q 1998 Elsevier Science B.V. .

Relaxing cochlear implant electrode design constraints using high pulse rate stimulation

Abstract: Inferior colliculus units have a significantly lower stimulus threshold when driven with a cochlear implant using bipolar stimuli at high (2 k pulses/s) compared to low (125 pulses/s) pulse rates. At high pulse rates temporal summation is used to explain this threshold shift. A background "spontaneous" stimulus strategy is described here which has the potential to lower further stimulus threshold current. Lower thresholds and smaller stimulus currents may allow for the use of smaller cochlear implant stimulus electrodes and potentially more channels of stimulation within a given cochlea region.