Mechanism, dynamics, and biological existence of multistability in a large class of bursting neurons

Multistability, the coexistence of multiple attractors in a dynamical system, is explored in bursting nerve cells. A modeling study is performed to show that a large class of bursting systems, as defined by a shared topology when represented as dynamical systems, is inherently suited to support multistability. We derive the bifurcation structure and parametric trends leading to multistability in these systems. Evidence for the existence of multirhythmic behavior in neurons of the aquatic mollusc Aplysia californica that is consistent with our proposed mechanism is presented. Although these experimental results are preliminary, they indicate that single neurons may be capable of dynamically storing information for longer time scales than typically attributed to nonsynaptic mechanisms.Comment: 24 pages, 8 figure

Rhythmogenesis and Bifurcation Analysis of 3-Node Neural Network Kernels

Central pattern generators (CPGs) are small neural circuits of coupled cells stably producing a range of multiphasic coordinated rhythmic activities like locomotion, heartbeat, and respiration. Rhythm generation resulting from synergistic interaction of CPG circuitry and intrinsic cellular properties remains deficiently understood and characterized. Pairing of experimental and computational studies has proven key in unlocking practical insights into operational and dynamical principles of CPGs, underlining growing consensus that the same fundamental circuitry may be shared by invertebrates and vertebrates. We explore the robustness of synchronized oscillatory patterns in small local networks, revealing universal principles of rhythmogenesis and multi-functionality in systems capable of facilitating stability in rhythm formation. Understanding principles leading to functional neural network behavior benefits future study of abnormal neurological diseases that result from perturbations of mechanisms governing normal rhythmic states. Qualitative and quantitative stability analysis of a family of reciprocally coupled neural circuits, constituted of generalized Fitzhugh–Nagumo neurons, explores symmetric and asymmetric connectivity within three-cell motifs, often forming constituent kernels within larger networks. Intrinsic mechanisms of synaptic release, escape, and post-inhibitory rebound lead to differing polyrhythmicity, where a single parameter or perturbation may trigger rhythm switching in otherwise robust networks. Bifurcation analysis and phase reduction methods elucidate qualitative changes in rhythm stability, permitting rapid identification and exploration of pivotal parameters describing biologically plausible network connectivity. Additional rhythm outcomes are elucidated, including phase-varying lags and broader cyclical behaviors, helping to characterize system capability and robustness reproducing experimentally observed outcomes. This work further develops a suite of visualization approaches and computational tools, describing robustness of network rhythmogenesis and disclosing principles for neuroscience applicable to other systems beyond motor-control. A framework for modular organization is introduced, using inhibitory and electrical synapses to couple well-characterized 3-node motifs described in this research as building blocks within larger networks to describe underlying cooperative mechanisms

Optical mapping and optogenetics in cardiac electrophysiology research and therapy:a state-of-the-art review

State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilizes light-sensitive ion channels and pumps to realize contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell–cell interactions. The merging of optogenetics and optical mapping techniques for ‘all-optical’ electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial–temporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturized, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimizing therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity, and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies

三次元心臓モデルと不均一振動モデルによる心臓活動電位のコンピュータシミュレーション

Tohoku University西條芳文論

Excitation model of cardiac p cells of the cardiac conduction system

The article considers elaboration of the mathematical model of cardiac electrical activity which will allow investigating excitation propagation processes at all sites of the cardiac conduction system. The proposed model is generated on the basis of parametric elements of an electric circuit with distributed parameters and approximation of time dependencies of conduction in ion channels by cubic splines

Dynamic clamp with StdpC software

Dynamic clamp is a powerful method that allows the introduction of artificial electrical components into target cells to simulate ionic conductances and synaptic inputs. This method is based on a fast cycle of measuring the membrane potential of a cell, calculating the current of a desired simulated component using an appropriate model and injecting this current into the cell. Here we present a dynamic clamp protocol using free, fully integrated, open-source software (StdpC, for spike timing-dependent plasticity clamp). Use of this protocol does not require specialist hardware, costly commercial software, experience in real-time operating systems or a strong programming background. The software enables the configuration and operation of a wide range of complex and fully automated dynamic clamp experiments through an intuitive and powerful interface with a minimal initial lead time of a few hours. After initial configuration, experimental results can be generated within minutes of establishing cell recording

Making Waves in the Brain: What Are Oscillations, and Why Modulating Them Makes Sense for Brain Injury.

Traumatic brain injury (TBI) can result in persistent cognitive, behavioral and emotional deficits. However, the vast majority of patients are not chronically hospitalized; rather they have to manage their disabilities once they are discharged to home. Promoting recovery to pre-injury level is important from a patient care as well as a societal perspective. Electrical neuromodulation is one approach that has shown promise in alleviating symptoms associated with neurological disorders such as in Parkinson's disease (PD) and epilepsy. Consistent with this perspective, both animal and clinical studies have revealed that TBI alters physiological oscillatory rhythms. More recently several studies demonstrated that low frequency stimulation improves cognitive outcome in models of TBI. Specifically, stimulation of the septohippocampal circuit in the theta frequency entrained oscillations and improved spatial learning following TBI. In order to evaluate the potential of electrical deep brain stimulation for clinical translation we review the basic neurophysiology of oscillations, their role in cognition and how they are changed post-TBI. Furthermore, we highlight several factors for future pre-clinical and clinical studies to consider, with the hope that it will promote a hypothesis driven approach to subsequent experimental designs and ultimately successful translation to improve outcome in patients with TBI