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1.
It is much debated on what time scale information is encoded by neuronal spike activity. With a phenomenological model that transforms time-dependent membrane potential fluctuations into spike trains, we investigate constraints for the timing of spikes and for synchronous activity of neurons with common input. The model of spike generation has a variable threshold that depends on the time elapsed since the previous action potential and on the preceding membrane potential changes. To ensure that the model operates in a biologically meaningful range, the model was adjusted to fit the responses of a fly visual interneuron to motion stimuli. The dependence of spike timing on the membrane potential dynamics was analyzed. Fast membrane potential fluctuations are needed to trigger spikes with a high temporal precision. Slow fluctuations lead to spike activity with a rate about proportional to the membrane potential. Thus, for a given level of stochastic input, the frequency range of membrane potential fluctuations induced by a stimulus determines whether a neuron can use a rate code or a temporal code. The relationship between the steepness of membrane potential fluctuations and the timing of spikes has also implications for synchronous activity in neurons with common input. Fast membrane potential changes must be shared by the neurons to produce synchronous activity.  相似文献   

2.
A fundamental issue in neuroscience is how to identify the multiple biophysical mechanisms through which neurons generate observed patterns of spiking activity. In previous work, we proposed a method for linking observed patterns of spiking activity to specific biophysical mechanisms based on a state space modeling framework and a sequential Monte Carlo, or particle filter, estimation algorithm. We have shown, in simulation, that this approach is able to identify a space of simple biophysical models that were consistent with observed spiking data (and included the model that generated the data), but have yet to demonstrate the application of the method to identify realistic currents from real spike train data. Here, we apply the particle filter to spiking data recorded from rat layer V cortical neurons, and correctly identify the dynamics of an slow, intrinsic current. The underlying intrinsic current is successfully identified in four distinct neurons, even though the cells exhibit two distinct classes of spiking activity: regular spiking and bursting. This approach – linking statistical, computational, and experimental neuroscience – provides an effective technique to constrain detailed biophysical models to specific mechanisms consistent with observed spike train data.  相似文献   

3.
Glycine is a classical inhibitory neurotransmitter however presynaptic glycine receptors have rather depolarizing action. Reasons for latter phenomenon are unknown. In the present paper we have investigated how glycine influences cytosolic chloride level monitored by fluorescent dye SPQ, membrane potential monitored by fluorescent dye DiSC3(5) and [14C]-glutamate release in synaptosomes. We estimated that cytosolic chloride concentration in synaptosomes was about 52 ± 1 mM. Glycine (1 mM) induced chloride efflux and caused slow plasma membrane depolarization. Chloride efflux was almost completely blocked by 100 μM strychnine whilst glycine-induced depolarization was only partially. We also showed that 1 mM glycine induced [14C]-glutamate release via a strychnine-insensitive pathway. Hence we have concluded that glycine was able to induce two independent effects in synaptosomes: (1) Chloride efflux with following depolarization. This efflux was sensitive to strychnine and thereby is probably conducted through glycine-gated ion channels. (2) Glutamate release seems to be mediated by glycine transporters.  相似文献   

4.
Estimation of the power spectrum is a common method for identifying oscillatory changes in neuronal activity. However, the stochastic nature of neuronal activity leads to severe biases in the estimation of these oscillations in single unit spike trains. Different biological and experimental factors cause the spike train to differentially reflect its underlying oscillatory rate function. We analyzed the effect of factors, such as the mean firing rate and the recording duration, on the detectability of oscillations and their significance, and tested these theoretical results on experimental data recorded in Parkinsonian non-human primates. The effect of these factors is dramatic, such that in some conditions, the detection of existing oscillations is impossible. Moreover, these biases impede the comparison of oscillations across brain regions, neuronal types, behavioral states and separate recordings with different underlying parameters, and lead inevitably to a gross misinterpretation of experimental results. We introduce a novel objective measure, the "modulation index", which overcomes these biases, and enables reliable detection of oscillations from spike trains and a direct estimation of the oscillation magnitude. The modulation index detects a high percentage of oscillations over a wide range of parameters, compared to classical spectral analysis methods, and enables an unbiased comparison between spike trains recorded from different neurons and using different experimental protocols.  相似文献   

5.
We describe a statistical technique, the joint peristimulus time (PST) scatter diagram, for the analysis of data from simultaneously recorded neurons subjected to repeated stimulation. Distinguishable features in the scatter diagram are related to effects of the stimulus on the observed neurons and to functional relations among the neurons. Properties of this measure and its variants are described and practical aspects of its application to experimental data are discussed.  相似文献   

6.
Constant current pulses have been applied to single muscle fibers of the barnacle, Balanus nubilus Darwin, with an axial metal electrode. The membrane potential change, which took place over a large part of the muscle fiber, was measured with a similar electrode. Depolarizing pulses, if the voltage was greater than threshold, produced tension. The size of the tension was a function of the magnitude and the duration of the depolarizing pulses. The latency between the onset of depolarization and tension can be only in part attributable to mechanical factors. AC stimulation produced tension, but 5 to 10 seconds were required for the steady-state level of the tension to be reached. Muscles were depolarized in elevated K and studied after the contracture had terminated. If not too depolarized, further depolarization produced tension. Termination of hyperpolarizing pulses also produced tension, which decayed quite slowly. Hyperpolarizing pulses reduced, or abolished, any preexisting tension. Thus, it appears that at certain values of the membrane potential tension is set up, but there is also a slow process of accommodation present.  相似文献   

7.
The responses of membrane potential and membrane resistanceof tonoplast-free Nitellopsis cells to step changes of internalpH (pHi) from 7 were studied during continuous perfusion withmedia containing either 1 mu ATP or no ATP. Whether ATP waspresent or not, the time course of Em responses was composedof an initial rapid change (initial phase) and a subsequentslow change (second phase). At the end of the second phase,Em attained nearly stable values. When Em values of ATP-containingcells obtained at the peak of the initial phase were plottedagainst pHi, Em was found to hyperpolarize most at pHi 6.5.This was also found for steady Em values measured at the endof the second phase. The Em values of ATP-lacking cells werealmost insensitive to pHi changes between 4 and 8, but morepositive than those of ATP-containing cells at pHi 4–7.5.Above pHi 8, no difference in Em was observed between the twotypes of cells. In this range of pHi, the Em change in the initialphase amounted to about 60 mV per unit of pHi change. The light-induced hyperpolarization still occurred at pHi 6.5where the electrogenic potential was maximal, and over the widepHi range, from 6.0 to 7.5 even when pHi was strongly buffered.Thus, we concluded that the pHi change may not be the causeof light-induced hyperpolarization. (Received December 5, 1983; Accepted June 18, 1984)  相似文献   

8.
The aim of this study is to evaluate directly, using a reduced experimental system, the nature of interactions between voltage-gated potassium channels and the resting membrane potential. Xenopus oocytes were injected with various concentrations of cRNA coding for a delayed-rectifier potassium channel Shaker-IR. The effects of the density and kinetics of the expressed channels on resting membrane potential is explored in isolated (``inside-out') patches. The channel density is given in terms of maximal conductance (G max), measured from the maximal slope of the I-V curve under voltage clamp conditions. The capacitance of the experimental setup is approximately 1 pF. At high channel densities (G max > 10 pA/mV) the mean membrane potential is stabilized at approximately −60 mV. This resting membrane potential is more than 35 mV positive to the reversal potential for potassium ions under the same experimental conditions. Analyses of voltage clamp experiments indicate that at high channel densities the mean membrane potential is determined by the rates of channel activation and deactivation, but is not affected by the rates involved in the process of slow (C-type) inactivation. In contrast, at lower channel densities membrane potential is very unstable, and its mean value and amplitude of fluctuations are strongly affected by the process of slow (C-type) inactivation. Received: 21 March 1996/Revised: 6 August 1996  相似文献   

9.
Phase Plane Trajectories of the Muscle Spike Potential   总被引:2,自引:0,他引:2       下载免费PDF全文
To facilitate a study of the transmembrane action current, the striated muscle spike potential was recorded against its first time derivative. The specialized recording methods are described, as well as several mathematical transformations between a coordinate system in V, t, and the present coordinate system in V, dV/dt. The particular properties of the present recording method permitted an estimation for the “sodium” potential in muscle fibers at +39 mv. The maximum membrane conductance during spike production is in the order of 150 to 200 mmhos/cm2. The changes in the shape of the recorded response indicate that the ionic currents and membrane conductances are reduced by Tris buffer or hypertonic Ringer's fluid. However, no marked changes in the properties of active membrane were observed when chloride ion was replaced by sulfate.  相似文献   

10.
Threshold fluctuations in axon firing can arise as a result of electrical noise in the excitable membrane. A general theoretical expression for the fluctuations is applied to the analysis of three sources of membrane noise: Johnson noise, excess 1/f noise, and sodium conductance fluctuations. Analytical expressions for the width of the firing probability curve are derived for each of these noise sources. Specific calculations are performed for the node of Ranvier of the frog, and attention is given to the manner in which threshold fluctuations are affected by variations of temperature, ion concentrations, and the application of various drugs. Comparison with existing data suggests that threshold fluctuations can best be explained by sodium conductance fluctuations. Additional experiments directed at distinguishing among the various noise sources are proposed.  相似文献   

11.
The release and uptake of neurotransmitters by synaptic vesicles is a tightly controlled process that occurs in response to diverse stimuli at morphologically disparate synapses. To meet these architectural and functional synaptic demands, it follows that there should be diversity in the mechanisms that control their secretion and retrieval and possibly in the composition of synaptic vesicles within the same terminal. Here we pay particular attention to areas where such diversity is generated, such as the variance in exocytosis/endocytosis coupling, SNAREs defining functionally diverse synaptic vesicle populations and the adaptor-dependent sorting machineries capable of generating vesicle diversity. We argue that there are various synaptic vesicle recycling pathways at any given synapse and discuss several lines of evidence that support the role of the endosome in synaptic vesicle recycling.Chemical synapses contain discrete numbers of synaptic vesicles, which are capable of sustaining neurotransmitter release. Sustained neurotransmission occurs despite the secretory demands imposed by persistent and diverse patterns of neuronal electrical activity. Maintaining synaptic vesicle numbers requires local mechanisms to regenerate these vesicles to prevent their exhaustion, preserve plasma membrane surface area, and to maintain the molecularly distinct identity of a vesicle versus plasma membrane. Rizzoli and Betz (2005) eloquently draw a parallel between chemical neurotransmission with synapse chatter saying that some synapses “whisper,” whereas others “shout.” The “louder” the synapse, the more synaptic vesicles are required, extending from a few hundred vesicles (whisperers) to nearly thousands (shouters). This beautiful analogy implies that every synapse has just one “voice” or species of vesicle. Here we will present the case that synapses are more like choirs in which multiple vesicle species or “voices” contribute to the “pianissimo” or “fortissimo” parts of chemical neurotransmission.Synaptic terminals show a range of structural and functional differences in distinct regions of the brain, suggesting that the mechanisms for exocytosis/endocytosis coupling, as well as local vesicle recycling, may also be diverse. On one side, the Calyx of Held nerve terminal participates in fast and sustained synaptic transmission at high frequency (800 Hz), which is crucial for sound localization in the auditory brainstem (Taschenberger and von Gersdorff 2000; Borst and Soria van Hoeve 2012). The Calyx of Held houses ∼70,000 synaptic vesicles with nearly 3000 vesicles docked per Calyx terminal. These docked vesicles are distributed across the ∼500 active zones that exist per Calyx where vesicle fusion occurs (Satzler et al. 2002). On the other hand, hippocampal synapses fire action potentials at ∼0.5 Hz in bursts (Dobrunz and Stevens 1999). This synapse contains ∼200 synaptic vesicles and one active zone with ∼10 vesicles docked (Schikorski and Stevens 1997). With such a wide functional and structural gamut of synapses, it is reasonable to hypothesize that synaptic vesicles may differ in their retrieval mechanisms, not just at the rate at which the process occurs but also in the molecular pathways used.Two synaptic vesicle retrieval mechanisms, namely clathrin/AP-2/dynamin-dependent biogenesis and kiss-and-run, have been summarized in outstanding recent reviews (see, for example, Augustine et al. 2006; Rizzoli and Jahn 2007; Smith et al. 2008; Royle and Lagnado 2010; Ferguson and De Camilli 2012; Saheki and De Camilli 2012). Therefore, here we focus on the coupling of secretion and membrane retrieval, as well as endosome sorting. We will discuss new developments supporting the existence of diverse functional and molecular pools of synaptic vesicles and how endocytosis and endosome retrieval mechanisms may generate these vesicle pools.  相似文献   

12.
Membrane potentials of cultured carrot cells in culture mediumwere about –40 mV and did not change with addition ofsalts of addition (or depletion) of 2,4-dichlorophenoxyaceticacid (2,4-D). When the measurement was performed in the testmedium (containing low concentration of salts), the values werewidely distributed (from –60 to –110mV) and changedlargely with external concentration of K+ but not Mg2+ nor Ca2+.When the cells were fractionated by Ficoll density gradientcentrifugation, the membrane potential of the cells of higherdensity (> 14% Ficoll) was about –150 mV in the testmedium and did not change during embryogenesis with depletionof 2,4-D. The membrane potential of cells of lower density (bandingbetween 6– 10% Ficoll) was less negative (– 60 to– 110 mV) in the test medium. When these cells were transferredand cultured in medium containing zeatin but lacking 2,4-D,the membrane potential was shifted negatively by about 15 mVprior to anthocyanin synthesis. When 2,4-D was added to anthocyanin-synthesizingcells in the medium containing zeatin, a transient hyperpolarizationand subsequent depolarization of the membrane were observedprior to the inhibition of anthocyanin synthesis. (Received October 22, 1987; Accepted April 20, 1988)  相似文献   

13.
The coronavirus membrane (M) protein is the key player in virion assembly. One of its functions is to mediate the incorporation of the spikes into the viral envelope. Heterotypic interactions between M and the spike (S) protein can be demonstrated by coimmunoprecipitation and by immunofluorescence colocalization, after coexpression of their genes in eukaryotic cells. Using these assays in a mutagenetic approach, we have mapped the domains in the M protein that are involved in complex formation between M and S. It appeared that the 25-residue luminally exposed amino-terminal domain of the M protein is not important for M-S interaction. A 15-residue deletion, the insertion of a His tag, and replacement of the ectodomain by that of another coronavirus M protein did not affect the ability of the M protein to associate with the S protein. However, complex formation was sensitive to changes in the transmembrane domains of this triple-spanning protein. Deletion of either the first two or the last two transmembrane domains, known not to affect the topology of the protein, led to a considerable decrease in complex formation, but association was not completely abrogated. Various effects of changes in the part of the M protein that is located at the cytoplasmic face of the membrane were observed. Deletions of the extreme carboxy-terminal tail appeared not to interfere with M-S complex formation. However, deletions in the amphipathic domain severely affected M-S interaction. Interestingly, changes in the amino-terminal and extreme carboxy-terminal domains of M, which did not disrupt the interaction with S, are known to be fatal to the ability of the protein to engage in virus particle formation (C. A. M. de Haan, L. Kuo, P. S. Masters, H. Vennema, and P. J. M. Rottier, J. Virol. 72:6838-6850, 1998). Apparently, the structural requirements of the M protein for virus particle assembly differ from the requirements for the formation of M-S complexes.  相似文献   

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为了通过研究不同长相穗型小麦穗部特性,以达到提高产量和挖掘穗部潜力的目的。本文对长方型、棍棒型、椭圆型和纺锤型四种不同长相穗型小麦品种的穗部性状特性进行了分析。结果表明不同穗型小麦在小花数、穗粒数、粒重等方面均表现出先升后降的二次曲线趋势,但不同穗型小麦表现趋势不同,长方型和椭圆型小麦在穗粒数、穗重、各粒位粒重等方面均优于棍棒型和纺锤型小麦,棍棒型小麦由于其特殊的穗型结构,在小穗密度、粒重等方面表现独特,纺锤型小麦在各方面表现均较差。结果表明,在小麦生产用种和品种选育上,穗型的选择至关重要。长方型小麦有提高小麦产量的潜力。  相似文献   

16.
Peptide-induced vesicle leakage is a common experimental test for the membrane-perturbing activity of antimicrobial peptides. The leakage kinetics is usually very slow, requiring minutes to hours for complete release of vesicle contents, and exhibits a biphasic behavior. We report here that, in the case of the peptaibol trichogin GA IV, all processes involved in peptide-membrane interaction, such as peptide-membrane association, peptide aggregation, and peptide translocation, take place on a timescale much shorter than the leakage kinetics. On the basis of these findings, we propose a stochastic model in which the leakage kinetics is determined by the discrete nature of a vesicle suspension: peptides are continuously exchanging among vesicles, producing significant fluctuations over time in the number of peptide molecules bound to each vesicle, and in the formation of pores. According to this model, the fast initial leakage is caused by vesicles that contain at least one pore after the peptides are randomly distributed among the liposomes, whereas the slower release is associated with the time needed to occasionally reach in an intact vesicle the critical number of bound peptides necessary for pore formation. Fluctuations due to peptide exchange among vesicles therefore represent the rate-limiting step of such a slow mechanism.  相似文献   

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《Molecular membrane biology》2013,30(1-2):155-168
Plasma membrane vesicles isolated from Ehrlich ascites tumor cells have been used to investigate the role of the transmembrane potential in the energetics of Systems A and L. As expected, Na+-dependent System A was responsive to changes in membrane potential. System L activity, as measured by transport of 2-aminonorbornane-2-carboxylic acid (BCH), was shown to be Na+-independent and was not altered by changes in the membrane potential. The combination of valinomycin and nigericin decreased accumulation of MeAIB but not that of BCH. The presence of nigericin alone caused a significant decrease in uptake by System A and a decrease in uptake by System L to a lesser degree. The inhibitory action of nigericin might reflect its ability to dissipate the Na+ gradient rather than an effect on K+ or H+ flows. The results indicate that modes of energization not produced through the transmembrane potential must account for any uphill operation of System L.  相似文献   

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