Continuation-based numerical detection of after-depolarization and spike-adding thresholds.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tThe changes in neuronal firing pattern are signatures of brain function, and it is of interest to understand how such changes evolve as a function of neuronal biophysical properties. We address this important problem by the analysis and numerical investigation of a class of mechanistic mathematical models. We focus on a hippocampal pyramidal neuron model and study the occurrence of bursting related to the after-depolarization (ADP) that follows a brief current injection. This type of burst is a transient phenomenon that is not amenable to the classical bifurcation analysis done, for example, for periodic bursting oscillators. In this letter, we show how to formulate such transient behavior as a two-point boundary value problem (2PBVP), which can be solved using well-known continuation methods. The 2PBVP is formulated such that the transient response is represented by a finite orbit segment for which onsets of ADP and additional spikes in a burst can be detected as bifurcations during a one-parameter continuation. This in turn provides us with a direct method to approximate the boundaries of regions in a two-parameter plane where certain model behavior of interest occurs. More precisely, we use two-parameter continuation of the detected onset points to identify the boundaries between regions with and without ADP and bursts with different numbers of spikes. Our 2PBVP formulation is a novel approach to parameter sensitivity analysis that can be applied to a wide range of problems.The research for this letter was done while J.N. was a Ph.D. student at the University of Bristol, supported by grant EP/E032249/1 from the Engineering and Physical Sciences Research Council (EPSRC). The research of K.T-A. was supported by EPSRC grant EP/I018638/1 and that of H.M.O. by grant UOA0718 of the Royal Society of NZ Marsden Fun

Bifurcation Analysis of a Two-Compartment Hippocampal Pyramidal Cell Model

The Pinsky-Rinzel model is a non-smooth 2-compartmental CA3 pyramidal cell model that has been used widely within the field of neuroscience. Here we propose a modified (smooth) system that captures the qualitative behaviour of the original model, while allowing the use of available, numerical continuation methods to perform full-system bifurcation and fastslow analysis. We study the bifurcation structure of the full system as a function of the applied current and the maximal calcium conductance. We identify the bifurcations that shape the transitions between resting, bursting and spiking behaviours, and which lead to the disappearance of bursting when the calcium conductance is reduced. Insights gained from this analysis, are then used to firstly illustrate how the irregular spiking activity found between bursting and stable spiking states, can be influenced by phase differences in the calcium and dendritic voltage, which lead to corresponding changes in the calcium-sensitive potassium current. Furthermore, we use fast-slow analysis to investigate the mechanisms of bursting and show that bursting in the model is dependent on the intermediately slow variable, calcium, while the other slow variable, the activation gate of the afterhyperpolarisation current, does not contribute to setting the intraburst dynamics but participates in setting the interburst interval. Finally, we discuss how some of the described bifurcations affect spiking behaviour, during sharp-wave ripples, in a larger network of Pinsky-Rinzel cells.LAA is supported by the Engineering and Physical Sciences Research Council (EPSRC) and Eli Lilly & Company; LYP is supported by the Wellcome Trust; and KT-A is supported by grant EP/N014391/1 of the EPSRC

Relaxation oscillations and canards in the Jirsa–Kelso excitator model: global flow perspective

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.Fenichel’s geometric singular perturbation theory and the blowup method have been very successful in describing and explaining global non-linear phenomena in systems with multiple time-scales, such as relaxation oscillations and canards. Recently, the blowup method has been extended to systems with flat, unbounded slow manifolds that lose normal hyperbolicity at infinity. Here, we show that transition between discrete and periodic movement captured by the Jirsa-Kelso excitator is a new example of such phenomena. We, first, derive equations of the Jirsa-Kelso excitator with explicit time scale separation and demonstrate existence of canards in the systems. Then, we combine the slow-fast analysis, blowup method and projection onto the the Poincar´e sphere to understand the return mechanism of the periodic orbits in the singular case, € = 0.KT-A gratefully acknowledges the financial support of the EPSRC via grant EP/N014391/1. This work was supported by The Higher Committee For Education Development in Iraq (HCED) and the University of Mosul