Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States

The phenomena that emerge from the interaction of the stochastic opening and closing of ion channels (channel noise) with the non-linear neural dynamics are essential to our understanding of the operation of the nervous system. The effects that channel noise can have on neural dynamics are generally studied using numerical simulations of stochastic models. Algorithms based on discrete Markov Chains (MC) seem to be the most reliable and trustworthy, but even optimized algorithms come with a non-negligible computational cost. Diffusion Approximation (DA) methods use Stochastic Differential Equations (SDE) to approximate the behavior of a number of MCs, considerably speeding up simulation times. However, model comparisons have suggested that DA methods did not lead to the same results as in MC modeling in terms of channel noise statistics and effects on excitability. Recently, it was shown that the difference arose because MCs were modeled with coupled activation subunits, while the DA was modeled using uncoupled activation subunits. Implementations of DA with coupled subunits, in the context of a specific kinetic scheme, yielded similar results to MC. However, it remained unclear how to generalize these implementations to different kinetic schemes, or whether they were faster than MC algorithms. Additionally, a steady state approximation was used for the stochastic terms, which, as we show here, can introduce significant inaccuracies. We derived the SDE explicitly for any given ion channel kinetic scheme. The resulting generic equations were surprisingly simple and interpretable - allowing an easy and efficient DA implementation. The algorithm was tested in a voltage clamp simulation and in two different current clamp simulations, yielding the same results as MC modeling. Also, the simulation efficiency of this DA method demonstrated considerable superiority over MC methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur

A perturbation analysis of spontaneous action potential initiation by stochastic ion channels

A stochastic interpretation of spontaneous action potential initiation is developed for the Morris- Lecar equations. Initiation of a spontaneous action potential can be interpreted as the escape from one of the wells of a double well potential, and we develop an asymptotic approximation of the mean exit time using a recently-developed quasi-stationary perturbation method. Using the fact that the activating ionic channel’s random openings and closings are fast relative to other processes, we derive an accurate estimate for the mean time to fire an action potential (MFT), which is valid for a below-threshold applied current. Previous studies have found that for above-threshold applied current, where there is only a single stable fixed point, a diffusion approximation can be used. We also explore why different diffusion approximation techniques fail to estimate the MFT

New Ideas for Brain Modelling

This paper describes some biologically-inspired processes that could be used to build the sort of networks that we associate with the human brain. New to this paper, a 'refined' neuron will be proposed. This is a group of neurons that by joining together can produce a more analogue system, but with the same level of control and reliability that a binary neuron would have. With this new structure, it will be possible to think of an essentially binary system in terms of a more variable set of values. The paper also shows how recent research associated with the new model, can be combined with established theories, to produce a more complete picture. The propositions are largely in line with conventional thinking, but possibly with one or two more radical suggestions. An earlier cognitive model can be filled in with more specific details, based on the new research results, where the components appear to fit together almost seamlessly. The intention of the research has been to describe plausible 'mechanical' processes that can produce the appropriate brain structures and mechanisms, but that could be used without the magical 'intelligence' part that is still not fully understood. There are also some important updates from an earlier version of this paper