736 research outputs found

    Bistable dynamics underlying excitability of ion homeostasis in neuron models

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    When neurons fire action potentials, dissipation of free energy is usually not directly considered, because the change in free energy is often negligible compared to the immense reservoir stored in neural transmembrane ion gradients and the long-term energy requirements are met through chemical energy, i.e., metabolism. However, these gradients can temporarily nearly vanish in neurological diseases, such as migraine and stroke, and in traumatic brain injury from concussions to severe injuries. We study biophysical neuron models based on the Hodgkin-Huxley (HH) formalism extended to include time-dependent ion concentrations inside and outside the cell and metabolic energy-driven pumps. We reveal the basic mechanism of a state of free energy-starvation (FES) with bifurcation analyses showing that ion dynamics is for a large range of pump rates bistable without contact to an ion bath. This is interpreted as a threshold reduction of a new fundamental mechanism of 'ionic excitability' that causes a long-lasting but transient FES as observed in pathological states. We can in particular conclude that a coupling of extracellular ion concentrations to a large glial-vascular bath can take a role as an inhibitory mechanism crucial in ion homeostasis, while the Na+^+/K+^+ pumps alone are insufficient to recover from FES. Our results provide the missing link between the HH formalism and activator-inhibitor models that have been successfully used for modeling migraine phenotypes, and therefore will allow us to validate the hypothesis that migraine symptoms are explained by disturbed function in ion channel subunits, Na+^+/K+^+ pumps, and other proteins that regulate ion homeostasis.Comment: 14 pages, 8 figures, 4 table

    Macroscopic equations governing noisy spiking neuronal populations

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    At functional scales, cortical behavior results from the complex interplay of a large number of excitable cells operating in noisy environments. Such systems resist to mathematical analysis, and computational neurosciences have largely relied on heuristic partial (and partially justified) macroscopic models, which successfully reproduced a number of relevant phenomena. The relationship between these macroscopic models and the spiking noisy dynamics of the underlying cells has since then been a great endeavor. Based on recent mean-field reductions for such spiking neurons, we present here {a principled reduction of large biologically plausible neuronal networks to firing-rate models, providing a rigorous} relationship between the macroscopic activity of populations of spiking neurons and popular macroscopic models, under a few assumptions (mainly linearity of the synapses). {The reduced model we derive consists of simple, low-dimensional ordinary differential equations with} parameters and {nonlinearities derived from} the underlying properties of the cells, and in particular the noise level. {These simple reduced models are shown to reproduce accurately the dynamics of large networks in numerical simulations}. Appropriate parameters and functions are made available {online} for different models of neurons: McKean, Fitzhugh-Nagumo and Hodgkin-Huxley models

    Multimodal transition and stochastic antiresonance in squid giant axons

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    The experimental data of N. Takahashi, Y. Hanyu, T. Musha, R. Kubo, and G. Matsumoto, Physica D \textbf{43}, 318 (1990), on the response of squid giant axons stimulated by periodic sequence of short current pulses is interpreted within the Hodgkin-Huxley model. The minimum of the firing rate as a function of the stimulus amplitude I0I_0 in the high-frequency regime is due to the multimodal transition. Below this singular point only odd multiples of the driving period remain and the system is highly sensitive to noise. The coefficient of variation has a maximum and the firing rate has a minimum as a function of the noise intensity which is an indication of the stochastic coherence antiresonance. The model calculations reproduce the frequency of occurrence of the most common modes in the vicinity of the transition. A linear relation of output frequency vs. I0I_0 for above the transition is also confirmed.Comment: 5 pages, 9 figure

    Effect of channel block on the spiking activity of excitable membranes in a stochastic Hodgkin-Huxley model

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    The influence of intrinsic channel noise on the spontaneous spiking activity of poisoned excitable membrane patches is studied by use of a stochastic generalization of the Hodgkin-Huxley model. Internal noise stemming from the stochastic dynamics of individual ion channels is known to affect the collective properties of the whole ion channel cluster. For example, there exists an optimal size of the membrane patch for which the internal noise alone causes a regular spontaneous generation of action potentials. In addition to varying the size of ion channel clusters, living organisms may adapt the densities of ion channels in order to optimally regulate the spontaneous spiking activity. The influence of channel block on the excitability of a membrane patch of certain size is twofold: First, a variation of ion channel densities primarily yields a change of the conductance level. Second, a down-regulation of working ion channels always increases the channel noise. While the former effect dominates in the case of sodium channel block resulting in a reduced spiking activity, the latter enhances the generation of spontaneous action potentials in the case of a tailored potassium channel blocking. Moreover, by blocking some portion of either potassium or sodium ion channels, it is possible to either increase or to decrease the regularity of the spike train.Comment: 10 pages, 3 figures, published 200

    Channel noise effects on neural synchronization

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    Synchronization in neural networks is strongly tied to the implementation of cognitive processes, but abnormal neuronal synchronization has been linked to a number of brain disorders such as epilepsy and schizophrenia. Here we examine the effects of channel noise on the synchronization of small Hodgkin-Huxley neuronal networks. The principal feature of a Hodgkin-Huxley neuron is the existence of protein channels that transition between open and closed states with voltage dependent rate constants. The Hodgkin-Huxley model assumes infinitely many channels, so fluctuations in the number of open channels do not affect the voltage. However, real neurons have finitely many channels which lead to fluctuations in the membrane voltage and modify the timing of the spikes, which may in turn lead to large changes in the degree of synchronization. We demonstrate that under mild conditions, neurons in the network reach a steady state synchronization level that depends only on the number of neurons in the network. The channel noise only affects the time it takes to reach the steady state synchronization level.Comment: 7 Figure

    An organizing center in a planar model of neuronal excitability

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    The paper studies the excitability properties of a generalized FitzHugh-Nagumo model. The model differs from the purely competitive FitzHugh-Nagumo model in that it accounts for the effect of cooperative gating variables such as activation of calcium currents. Excitability is explored by unfolding a pitchfork bifurcation that is shown to organize five different types of excitability. In addition to the three classical types of neuronal excitability, two novel types are described and distinctly associated to the presence of cooperative variables
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