Showing papers on "Summation published in 2008"

Complex Events Initiated by Individual Spikes in the Human Cerebral Cortex

Abstract: Synaptic interactions between neurons of the human cerebral cortex were not directly studied to date. We recorded the first dataset, to our knowledge, on the synaptic effect of identified human pyramidal cells on various types of postsynaptic neurons and reveal complex events triggered by individual action potentials in the human neocortical network. Brain slices were prepared from nonpathological samples of cortex that had to be removed for the surgical treatment of brain areas beneath association cortices of 58 patients aged 18 to 73 y. Simultaneous triple and quadruple whole-cell patch clamp recordings were performed testing mono- and polysynaptic potentials in target neurons following a single action potential fired by layer 2/3 pyramidal cells, and the temporal structure of events and underlying mechanisms were analyzed. In addition to monosynaptic postsynaptic potentials, individual action potentials in presynaptic pyramidal cells initiated long-lasting (37 ± 17 ms) sequences of events in the network lasting an order of magnitude longer than detected previously in other species. These event series were composed of specifically alternating glutamatergic and GABAergic postsynaptic potentials and required selective spike-to-spike coupling from pyramidal cells to GABAergic interneurons producing concomitant inhibitory as well as excitatory feed-forward action of GABA. Single action potentials of human neurons are sufficient to recruit Hebbian-like neuronal assemblies that are proposed to participate in cognitive processes.

Spatial Summation Can Explain the Attentional Modulation of Neuronal Responses to Multiple Stimuli in Area V4

Abstract: Although many studies have shown that the activity of individual neurons in a variety of visual areas is modulated by attention, a fundamental question remains unresolved: can attention alter the visual representations of individual neurons? One set of studies, primarily relying on the attentional modulations observed when a single stimulus is presented within the receptive field of a neuron, suggests that neuronal selectivities, such as orientation or direction tuning, are not fundamentally altered by attention (Salinas and Abbott, 1997; McAdams and Maunsell, 1999; Treue and Martinez Trujillo, 1999). Another set of studies, relying on modulations observed when multiple stimuli are presented within a receptive field, suggests that attention can alter the weighting of sensory inputs (Moran and Desimone, 1985; Luck et al., 1997; Reynolds et al., 1999; Chelazzi et al., 2001). In these studies, when preferred and nonpreferred stimuli are simultaneously presented, responses are much stronger when attention is directed to the preferred stimulus than when it is directed to the nonpreferred stimulus. In this study, we recorded neuronal responses from individual neurons in visual cortical area V4 to both single and paired stimuli with a variety of attentional allocations and stimulus combinations. For each neuron studied, we constructed a quantitative model of input summation and then tested various models of attention. In many neurons, we are able to explain neuronal responses across the entire range of stimuli and attentional allocations tested. Specifically, we are able to reconcile seemingly inconsistent observations of single and paired stimuli attentional modulation with a new model in which attention can facilitate or suppress specific inputs to a neuron but does not fundamentally alter the integration of these inputs.

Information-Processing Channels in the Tactile Sensory System: A Psychophysical and Physiological Analysis

Abstract: Channels in touch -- Identification of specific neural systems responsible for mechanoreception -- Duplex model of mechanoreception -- Spatial and temporal summation in the P system -- The neural bases of the tactile systems -- Anatomy of tactile receptors -- Neurophysiology of tactile receptors and their nerve fibers -- Neural bases of the P and NP systems -- Four neural systems mediate the detection of vibratory stimuli -- Frequency selectivity of a neural system is determined by its receptors -- From neural systems to information-processing channels -- Sensation-magnitude enhancement occurs within but not across channels -- Multichannel model of tactile sensitivity -- The psychophysical tuning curve -- Testing the multichannel model through experiments on adaptation and masking -- Adaptation reveals the existence of tactile channels -- Masking occurs within but not across channels -- Testing the multichannel model through experiments on sensory learning -- Properties of tactile channels -- The frequency selectivity of channels -- Temporal summation and temporal acuity -- Spatial acuity -- Edge detection -- Spatial summation -- Effects of observer characteristics -- Effects of aging on the sensitivity of tactile channels -- Effects of the menstrual cycle -- The functional roles of channels -- Channels enhance the detectability of stimuli -- Channels enhance the discriminability of stimuli -- The functional roles of the individual tactile channels -- The decibel scale -- The functional role of the PC channel -- The functional role of the RA channel -- The functional role of the SA I channel -- The functional role of the SA II channel -- Specialization of channels -- Channel interactions -- Summation of sensation magnitude across channels -- The perception of texture -- Role of attention in the enhancement and summation of sensation magnitude -- Interactions between tactile channels and other somatosensory submodalities.

The effects of DNIC-type inhibition on temporal summation compared to single pulse processing: does sex matter?

Abstract: A few experimental observations have suggested that diffuse noxious inhibitory control (DNIC)-type inhibition acts preferentially on the pain system if this is in a sensitised state, e.g. after slow temporal summation (wind-up). However, firm evidence is still missing. Furthermore, sex-related factors, which seem to affect temporal summation as well as DNIC effects, might thus also modulate the interaction of these two processes. To answer these questions, we investigated 40 young and pain-free subjects (20 female and 20 male). The conditioning stimulus in our DNIC paradigm was realized by immersion of the hand into a water tub containing either 42 degrees C (non-painful heat) or 46 degrees C (painful heat) hot water. The test stimuli were either single pulses or series of five pulses (0.5 Hz repetition frequency) produced by a pressure algometer. The VAS ratings for the last stimulus in the series were significantly higher than for the single pulse (temporal summation). The ratings were significantly reduced by the 42 degrees C conditioning stimulus and even more by the 46 degrees C conditioning stimulus, suggesting DNIC-like inhibition. This was equally true both for the single pulse and for the series of pulses. Sex differences were not observed for temporal summation, DNIC inhibition or for the interaction of the two processes, although women exhibited significantly lower pressure pain thresholds and higher ratings for the tonic heat stimuli. In conclusion, DNIC-type inhibition apparently does not preferentially act on a sensitised pain system after slow temporal summation. Considering the sex of the subjects does not change this insight.

Intrinsic Conductances Actively Shape Excitatory and Inhibitory Postsynaptic Responses in Olfactory Bulb External Tufted Cells

Abstract: The initial synapse in the olfactory system is from olfactory nerve (ON) terminals to postsynaptic targets in olfactory bulb glomeruli. Recent studies have disclosed multiple presynaptic factors that regulate this important linkage, but less is known about the contribution of postsynaptic intrinsic conductances to integration at these synapses. The present study demonstrates voltage-dependent amplification of EPSPs in external tufted (ET) cells in response to monosynaptic (ON) inputs. This amplification is mainly exerted by persistent Na(+) conductance. Larger EPSPs, which bring the membrane potential to a relatively depolarized level, are further boosted by the low-voltage-activated Ca(2+) conductance. In contrast, the hyperpolarization-activated nonselective cation conductance (I(h)) attenuates EPSPs mainly by reducing EPSP duration; this also reduces temporal summation of multiple EPSPs. Regulation of EPSPs by these subthreshold, voltage-dependent conductances can enhance both the signal-to-noise ratio and the temporal summation of multiple synaptic inputs and thus help ET cells differentiate high- and low-frequency synaptic inputs. I(h) can also transform inhibitory inputs to postsynaptic excitation. When the ET cell membrane potential is relatively depolarized, as during a burst of action potentials, IPSPs produce classic inhibition. However, near resting membrane potentials where I(h) is engaged, IPSPs produce rebound bursts of action potentials. ET cells excite GABAergic PG cells. Thus, the transformation of inhibitory inputs to postsynaptic excitation in ET cells may enhance intraglomerular inhibition of mitral/tufted cells, the main output neurons in the olfactory bulb, and hence shape signaling to olfactory cortex.

A role for wind‐up in trigeminal sensory processing: intensity coding of nociceptive stimuli in the rat

Abstract: Wind-up is a progressive, frequency-dependent increase in the excitability of trigeminal and spinal dorsal horn wide dynamic range (WDR) nociceptive neurons evoked by repetitive stimulation of primary afferent nociceptive C-fibres. The correlate of wind-up in humans is temporal summation, which is an increase in pain perception to repetitive constant nociceptive stimulation. Although wind-up is widely used as a tool for studying the processing of nociceptive information, including central sensitization, its actual role is still unknown. Here, we recorded from trigeminal WDR neurons using in vivo electrophysiological techniques in rats and assessed the wind-up phenomenon in response to stimuli of different intensities and frequencies. First, we found that the amplitude of C-evoked responses of WDR neurons to repetitive stimulation increased progressively to reach a peak, then consistently showed a stable or slightly decreasing plateau phase. Only the first phase of this time course fitted in with the wind-up description. Therefore, to assess wind-up, we measured a limited number of initial responses. Second, we showed that wind-up, i.e. the slope of the frequency-dependent increase in the response to C-fibre stimulation, was linearly correlated to the stimulus intensity. Intensities of brief C-fibre inputs were thus coded into frequencies of action potentials by second-order neurons through frequency-dependent potentiation of the evoked responses. Third, wind-up also occurred at stimulation intensities below the threshold for C-evoked responses in WDR neurons, suggesting that wind-up can amplify subthreshold C-fibre inputs to WDR neurons. This might account for the observation that sparse, subliminal, neuronal activity in nociceptors can become painful via central integration of neural responses. Altogether, the present results show that wind-up can provide trigeminal WDR neurons with the capability to encode the intensity of short-duration orofacial nociceptive stimuli and to detect subthreshold nociceptive input. Thus, not only may wind-up play a physiological role in trigeminal sensory processing, but its enhancement may also underlie the pathophysiology of chronic orofacial pain conditions.

Summation of excitatory and inhibitory synaptic inputs by motoneurons with highly active dendrites

Abstract: We investigated summation of steady excitatory and inhibitory inputs in spinal motoneurons using an in vivo preparation, the decerebrate cat, in which neuromodulatory input from the brain stem facilitated a strong persistent inward current (PIC) in dendritic regions. This dendritic PIC amplified both excitatory and inhibitory synaptic currents two- to threefold, but within different voltage ranges. Amplification of excitatory synaptic current peaked at voltage-clamp holding potentials near spike threshold (about -55 to -50 mV), whereas amplification of inhibitory current peaked at significantly more depolarized levels (about -45 to -40 mV). Thus the linear sum of excitatory and inhibitory currents tended to vary from net excitatory to net inhibitory as holding potential was depolarized. The actual summed currents, however, diverged from the predicted linear currents. At the peak of excitation, summation averaged about 15% sublinear (actual sum was less positive than the linear sum). In contrast, at the peak of inhibition, summation averaged about 18% supralinear (actual more positive than linear). Moreover, these nonlinear effects were substantially larger in cells where the variation from peak excitation to peak inhibition for linear summation was larger. When descending neuromodulatory input was eliminated by acute spinalization, PIC amplification was not observed and summation tended to be either sublinear or approximately linear, depending on input source. Overall, in cells with strong PICs, nonlinear summation of excitation and inhibition does occur, but this nonlinearity results in a more consistent relationship between membrane potential and the summed excitatory and inhibitory current.

Contrast-Dependent and Contrast-Independent Spatial Summation of Primary Visual Cortical Neurons of the Cat

Abstract: Recent studies have reported that the size of the classical receptive field (CRF) and the extent of spatial summation of V1 neurons depend on stimulus contrast. We reexamined these properties for 48 V1 neurons in the cat and found that all the cells had a constant CRF size, whereas their spatial summation properties can be contrast dependent (CD) or contrast independent (CID). Of the 29 CD cells, 17 showed facilitatory summation at low contrast (10%), but suppressive summation at high contrast (80%); the other 12 showed weak suppressive summation at low contrast, whereas the strength of suppression increased significantly at high contrast. The 19 CID cells showed similar facilitative (CIDf) or suppressive (CIDs) summation at low and high contrast, without changes in shape and/or peak location. We successfully labeled 11 CD cells and 10 CID cells with biocytin. The morphological results demonstrated that all the labeled CD cells were pyramidal cells, whereas all labeled CID cells were nonpyramidal cells, in which the CIDf cells were spiny stellates and the CIDs cells, smooth interneurons. There is thus a global distinction between summation properties of pyramidal and nonpyramidal cells, and between the smooth and spiny nonpyramidal cells as well.

Paired-pulse depression of excitatory postsynaptic current sinks in hippocampal CA1 in vivo.

Abstract: Paired-pulse depression (PPD), a short-term neural plasticity, was studied in hippocampal CA1 of urethane-anesthetized rats in vivo, using field potential recordings and current source density analysis PPD was robust when an ipsilateral CA3 (iCA3) conditioning pulse of moderate stimulus intensity was followed 30-200 ms later by a contralateral CA3 (cCA3) test pulse; the ratio of the conditioned (C) to the nonconditioned (NC) response, as measured by the peak excitatory sink at the apical dendrites, ranged from 06 to 08 An alveus conditioning pulse evoked a large antidromic population spike in CA1 and a modest depression of the CA3-evoked excitatory sink (C/NC ratio of approximately 085) High-intensity paired pulses, both delivered to iCA3, also showed PPD of the proximal excitatory sinks; however, paired-pulse facilitation of the dendritic sinks was found at the mid-apical dendrites, >250 microm from the soma Local injection of GABA(A) antagonist picrotoxin or bicuculline increased the C/NC ratio at IPIs of <150 ms, as well as the ratio of the amplitude of the population spikes (P2/P1; where P2 and P1 are the population spikes evoked by the second and first pulse, respectively) GABA(B) receptor antagonists, CGP35348 given intracerebroventricularly or CGP56999A administered locally, increased C/NC and P2/P1 at IPIs of 150-400 ms It is concluded that conditioned depression of the excitatory sinks was caused by mainly feedforward and some feedback inhibition at the apical dendrites GABA(A)-mediated postsynaptic inhibition dominated at early latencies, while GABA(B)-mediated inhibition prevailed at long latencies, probably at both presynaptic and postsynaptic sites PPD of the excitatory sinks provides a measure of population dendritic inhibition in vivo

Two differential frequency-dependent mechanisms regulating tonic firing of thalamic reticular neurons.

Abstract: Transmission through the thalamus activates circuits involving the GABAergic neurons of the thalamic reticular nucleus (TRN). TRN cells receive excitatory inputs from thalamocortical and corticothalamic cells and send inhibitory projections to thalamocortical cells. The inhibitory output of TRN neurons largely depends on the level of excitatory drive to these cells but may also be partly under the control of mechanisms intrinsic to the TRN. We examined two such possible mechanisms, short-term plasticity at glutamatergic synapses in the TRN and intra-TRN inhibition. In rat brain slices, responses of TRN neurons to brief trains of stimuli applied to glutamatergic inputs were recorded in voltage- or current-clamp mode. In voltage clamp, TRN cells showed no change in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor-mediated excitatory postsynaptic current amplitudes to stimulation at non-gamma frequencies ( 30 Hz), simulating sensory transmission. In current clamp, TRN cells increased their spike outputs in burst and tonic firing modes to increasing stimulus-train frequencies. These increases in spike output were most likely due to temporal summation of excitatory postsynaptic potentials. However, the frequency-dependent increase in tonic firing was attenuated at gamma stimulus frequencies, indicating that the synaptic depression selectively observed in this frequency range acts to suppress TRN cell output. In contrast, intra-TRN inhibition reduced spike output selectively at non-gamma stimulus frequencies. Thus, our data indicate that two intrinsic mechanisms play a role in controlling the tonic spike output of TRN neurons and these mechanisms are differentially related to two physiologically meaningful stimulus frequency ranges.

The Effect of Acupuncture on Temporal Summation of Pain: A Randomised, Double-Blind, Sham-Controlled Study

Abstract: BACKGROUND: The analgesic effects of manual acupuncture (MA) and electro-acupuncture (EA) have been studied in healthy humans and patients with pain. The advantage of studying pain in healthy humans is that the intensity of stimulation can be accurately c

How the nonlinear voltage dependence of the amplitude of excitatory postsynaptic potentials induced by cerebral cortical neurons affects cortical rhythmic activity

Abstract: A nonlinear dependence of the amplitude of excitatory postsynaptic potentials on the membrane potentials was derived. The existence of a region of oscillation stability with an increase in the mean value of nonspecific afferent inflow was demonstrated. A high-frequency oscillation component (40–60 Hz) appears with a pronounced increase in the afferent inflow; this can cause instability in oscillations and abnormal brain activity.