Localization of sound source azimuth within horizontal plane uses interaural time differences (ITDs) between sounds arriving through the left and right ear. In mammals, ITDs are processed primarily in the medial superior olive (MSO) neurons. These are the first binaural neurons in the auditory pathway. The MSO neurons are notable because they possess high time precision in the range of tens of microseconds. Several theories and experimental studies explain how neurons are able to achieve such precision. In most theories, neuronal coincidence detection processes the ITDs and encodes azimuth in ascending neurons of the auditory pathway using modalities that are more tractable than the ITD. These modalities have been described as firing rate codes, place codes (labeled line codes) and similarly. In this theoretical model it is described how the ITD is processed by coincidence detection and converted into spikes by summing the postsynaptic potentials. Particular postsynaptic conductance functions are used in order to obtain an analytical solution in a closed form. Specifically, postsynaptic response functions are derived from the exponential decay of postsynaptic conductances and the MSO neuron is modeled as a simplified version of the Spike Response Model (SRM0) which uses linear summations of the membrane responses to synaptic inputs. For plausible ratios of time constants, an analytical solution used to describe properties of coincidence detection window is obtained. The parameter space is then explored in the vicinity of the analytical solution. The variation of parameters does not change the solution qualitatively.

• MeSH
• akční potenciály fyziologie   MeSH
• lidé MeSH
• lokalizace zvuku fyziologie   MeSH
• modely neurologické * MeSH
• nervová síť fyziologie   MeSH
• nervové receptory fyziologie   MeSH
• nervový přenos fyziologie   MeSH
• počítačová simulace MeSH
• sluchová dráha fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Epilepsy presurgical investigation may include focal intracortical single-pulse electrical stimulations with depth electrodes, which induce cortico-cortical evoked potentials at distant sites because of white matter connectivity. Cortico-cortical evoked potentials provide a unique window on functional brain networks because they contain sufficient information to infer dynamical properties of large-scale brain connectivity, such as preferred directionality and propagation latencies. Here, we developed a biologically informed modelling approach to estimate the neural physiological parameters of brain functional networks from the cortico-cortical evoked potentials recorded in a large multicentric database. Specifically, we considered each cortico-cortical evoked potential as the output of a transient stimulus entering the stimulated region, which directly propagated to the recording region. Both regions were modelled as coupled neural mass models, the parameters of which were estimated from the first cortico-cortical evoked potential component, occurring before 80 ms, using dynamic causal modelling and Bayesian model inversion. This methodology was applied to the data of 780 patients with epilepsy from the F-TRACT database, providing a total of 34 354 bipolar stimulations and 774 445 cortico-cortical evoked potentials. The cortical mapping of the local excitatory and inhibitory synaptic time constants and of the axonal conduction delays between cortical regions was obtained at the population level using anatomy-based averaging procedures, based on the Lausanne2008 and the HCP-MMP1 parcellation schemes, containing 130 and 360 parcels, respectively. To rule out brain maturation effects, a separate analysis was performed for older (>15 years) and younger patients (<15 years). In the group of older subjects, we found that the cortico-cortical axonal conduction delays between parcels were globally short (median = 10.2 ms) and only 16% were larger than 20 ms. This was associated to a median velocity of 3.9 m/s. Although a general lengthening of these delays with the distance between the stimulating and recording contacts was observed across the cortex, some regions were less affected by this rule, such as the insula for which almost all efferent and afferent connections were faster than 10 ms. Synaptic time constants were found to be shorter in the sensorimotor, medial occipital and latero-temporal regions, than in other cortical areas. Finally, we found that axonal conduction delays were significantly larger in the group of subjects younger than 15 years, which corroborates that brain maturation increases the speed of brain dynamics. To our knowledge, this study is the first to provide a local estimation of axonal conduction delays and synaptic time constants across the whole human cortex in vivo, based on intracerebral electrophysiological recordings.

• MeSH
• Bayesova věta MeSH
• elektrická stimulace metody   MeSH
• epilepsie * MeSH
• evokované potenciály * fyziologie   MeSH
• lidé MeSH
• mapování mozku metody   MeSH
• mozek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

We study optimal estimation of a signal in parametric neuronal models on the basis of interspike interval data. Fisher information is the inverse asymptotic variance of the best estimator. Its dependence on the parameter value indicates accuracy of estimation. Our models assume that the input signal is estimated from neuronal output interspike interval data where the frequency transfer function is sigmoidal. If the coefficient of variation of the interspike interval is constant with respect to the signal, the Fisher information is unimodal, and its maximum for the most estimable signal can be found. We obtain a general result and compare the signal producing maximal Fisher information with the inflection point of the sigmoidal transfer function in several basic neuronal models.

• MeSH
• akční potenciály fyziologie   MeSH
• časové faktory MeSH
• entropie MeSH
• financování vládou MeSH
• modely neurologické MeSH
• nervový přenos genetika   MeSH
• nervový útlum MeSH
• neurony fyziologie   MeSH
• počítačová simulace MeSH
• Poissonovo rozdělení MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH

N-methyl-d-aspartate (NMDA) receptors (NMDARs) are highly expressed in the CNS and mediate the slow component of excitatory transmission. The present study was aimed at characterizing the temperature dependence of the kinetic properties of native NMDARs, with special emphasis on the deactivation of synaptic NMDARs. We used patch-clamp recordings to study synaptic NMDARs at layer II/III pyramidal neurons of the rat cortex, recombinant GluN1/GluN2B receptors expressed in human embryonic kidney (HEK293) cells, and NMDARs in cultured hippocampal neurons. We found that time constants characterizing the deactivation of NMDAR-mediated excitatory postsynaptic currents (EPSCs) were similar to those of the deactivation of responses to a brief application of glutamate recorded under conditions of low NMDAR desensitization (whole-cell recording from cultured hippocampal neurons). In contrast, the deactivation of NMDAR-mediated responses exhibiting a high degree of desensitization (outside-out recording) was substantially faster than that of synaptic NMDA receptors. The time constants characterizing the deactivation of synaptic NMDARs and native NMDARs activated by exogenous glutamate application were only weakly temperature sensitive (Q(10)=1.7-2.2), in contrast to those of recombinant GluN1/GluN2B receptors, which are highly temperature sensitive (Q(10)=2.7-3.7). Ifenprodil reduced the amplitude of NMDAR-mediated EPSCs by approximately 50% but had no effect on the time course of deactivation. Analysis of GluN1/GluN2B responses indicated that the double exponential time course of deactivation reflects mainly agonist dissociation and receptor desensitization. We conclude that the temperature dependences of native and recombinant NMDAR are different; in addition, we contribute to a better understanding of the molecular mechanism that controls the time course of NMDAR-mediated EPSCs. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

• MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• buněčné linie MeSH
• excitační postsynaptické potenciály fyziologie   účinky léků   MeSH
• hipokampus fyziologie   účinky léků   MeSH
• kinetika MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• kyselina glutamová metabolismus   MeSH
• lidé MeSH
• mozková kůra fyziologie   účinky léků   MeSH
• nervový přenos fyziologie   účinky léků   MeSH
• piperidiny farmakologie   MeSH
• potkani Wistar MeSH
• pyramidové buňky fyziologie   účinky léků   MeSH
• receptory N-methyl-D-aspartátu metabolismus   MeSH
• synapse fyziologie   účinky léků   MeSH
• techniky in vitro MeSH
• teplota MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH

• MeSH
• elektrodiagnostika metody   MeSH
• elektromyografie MeSH
• nemoci míchy diagnóza   MeSH
• nervové vedení fyziologie   MeSH
• nervový přenos fyziologie   MeSH
• neuromuskulární nemoci diagnóza   MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• diagnostika
• NLK Publikační typ
• kolektivní monografie

Five parameters of one of the most common neuronal models, the diffusion leaky integrate-and-fire model, also known as the Ornstein-Uhlenbeck neuronal model, were estimated on the basis of intracellular recording. These parameters can be classified into two categories. Three of them (the membrane time constant, the resting potential and the firing threshold) characterize the neuron itself. The remaining two characterize the neuronal input. The intracellular data were collected during spontaneous firing, which in this case is characterized by a Poisson process of interspike intervals. Two methods for the estimation were applied, the regression method and the maximum-likelihood method. Both methods permit to estimate the input parameters and the membrane time constant in a short time window (a single interspike interval). We found that, at least in our example, the regression method gave more consistent results than the maximum-likelihood method. The estimates of the input parameters show the asymptotical normality, which can be further used for statistical testing, under the condition that the data are collected in different experimental situations. The model neuron, as deduced from the determined parameters, works in a subthreshold regimen. This result was confirmed by both applied methods. The subthreshold regimen for this model is characterized by the Poissonian firing. This is in a complete agreement with the observed interspike interval data.

• MeSH
• akční potenciály fyziologie   MeSH
• buněčná membrána fyziologie   MeSH
• financování organizované MeSH
• lidé MeSH
• mozek fyziologie   MeSH
• nervové dráhy fyziologie   MeSH
• nervový přenos fyziologie   MeSH
• neuronové sítě MeSH
• neurony fyziologie   MeSH
• počítačové zpracování signálu MeSH
• Poissonovo rozdělení MeSH
• stochastické procesy MeSH
• synapse fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

NMDA receptors (NMDARs) are glutamate-gated ion channels that mediate excitatory neurotransmission in the CNS. Although these receptors are in direct contact with plasma membrane, lipid-NMDAR interactions are little understood. In the present study, we aimed at characterizing the effect of cholesterol on the ionotropic glutamate receptors. Whole-cell current responses induced by fast application of NMDA in cultured rat cerebellar granule cells (CGCs) were almost abolished (reduced to 3%) and the relative degree of receptor desensitization was increased (by seven-fold) after acute cholesterol depletion by methyl-β-cyclodextrin. Both of these effects were fully reversible by cholesterol repletion. By contrast, the responses mediated by AMPA/kainate receptors were not affected by cholesterol depletion. Similar results were obtained in CGCs after chronic inhibition of cholesterol biosynthesis by simvastatin and acute enzymatic cholesterol degradation to 4-cholesten-3-one by cholesterol oxidase. Fluorescence anisotropy measurements showed that membrane fluidity increased after methyl-β-cyclodextrin pretreatment. However, no change in fluidity was observed after cholesterol enzymatic degradation, suggesting that the effect of cholesterol on NMDARs is not mediated by changes in membrane fluidity. Our data show that diminution of NMDAR responses by cholesterol depletion is the result of a reduction of the open probability, whereas the increase in receptor desensitization is the result of an increase in the rate constant of entry into the desensitized state. Surface NMDAR population, agonist affinity, single-channel conductance and open time were not altered in cholesterol-depleted CGCs. The results of our experiments show that cholesterol is a strong endogenous modulator of NMDARs.

• MeSH
• anticholesteremika farmakologie   MeSH
• beta-cyklodextriny farmakologie   MeSH
• cholesterol oxidasa farmakologie   MeSH
• cholesterol nedostatek   fyziologie   MeSH
• elektrofyziologické jevy fyziologie   MeSH
• fluidita membrány účinky léků   fyziologie   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• membránové lipidy fyziologie   MeSH
• metoda terčíkového zámku MeSH
• mozeček cytologie   účinky léků   fyziologie   MeSH
• nervové vedení fyziologie   MeSH
• nervový přenos fyziologie   MeSH
• potkani Wistar MeSH
• receptory N-methyl-D-aspartátu účinky léků   fyziologie   MeSH
• simvastatin farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• mozek MeSH
• neurofyziologie MeSH
• neurony MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• neurologie
• neurovědy

• Konspekt
• Biologické vědy
• NLK Obory
• biologie
• fyziologie

N-methyl-D-aspartate (NMDA) receptors are highly expressed in the CNS, mediate the slow component of excitatory transmission and play key roles in synaptic plasticity and excitotoxicity. These ligand-gated ion channels are heteromultimers composed of NR1 and NR2 subunits activated by glycine and glutamate. In this study, patch-clamp recordings were used to study the temperature sensitivity of recombinant NR1/NR2B receptors expressed in human embryonic kidney (HEK) 293 cells. Rate constants were assessed by fitting a six-state kinetic scheme to time courses of transient macroscopic currents induced by glutamate at 21.9-46.5 degrees C. Arrhenius transformation of the rate constants characterizing NMDA receptor channel activity indicates that the most sensitive were the rate constants of desensitization (temperature coefficient Q(10)=10.3), resensitization (Q(10)=4.6) and unbinding (Q(10)=3.6). Other rate constants and the amplitude of single-channel currents were less temperature sensitive. Deactivation of responses mediated by NR1/NR2B receptors after a brief application of glutamate was best fit by a double exponential function (tau(fast): Q(10)=3.7; tau(slow): Q(10)=2.7). From these data, we conclude that desensitization/resensitization of the NMDA receptor and glutamate unbinding are especially temperature sensitive and imply that at physiological temperatures the channel kinetics play an important role in determining amplitude and time course of NMDA receptor-mediated postsynaptic currents and these receptors mediated synaptic plasticity.

• MeSH
• algoritmy MeSH
• buněčné linie MeSH
• elektrofyziologie MeSH
• financování organizované MeSH
• gating iontového kanálu fyziologie   MeSH
• kinetika MeSH
• kyselina glutamová metabolismus   MeSH
• ledviny cytologie   metabolismus   MeSH
• lidé MeSH
• metoda terčíkového zámku MeSH
• receptory N-methyl-D-aspartátu fyziologie   genetika   účinky léků   MeSH
• rekombinantní proteiny MeSH
• statistické modely MeSH
• techniky in vitro MeSH
• teplota MeSH
• transfekce MeSH
• Check Tag
• lidé MeSH