Many features of the sequence of action potentials produced by repeated stimulation of a patch of cardiac muscle can be modeled by a 1D mapping, but not the full behavior included in the restitution portrait. Specifically, recent experiments have found that (i) the dynamic and S1-S2 restitution curves are different (rate dependence) and (ii) the approach to steady state, which requires many action potentials (accommodation), occurs along a curve distinct from either restitution curve. Neither behavior can be produced by a 1D mapping. To address these shortcomings, ad hoc 2D mappings, where the second variable is a "memory" variable, have been proposed; these models exhibit qualitative features of the relevant behavior, but a quantitative fit is not possible. In this paper we introduce a new 2D mapping and determine a set of parameters for it that gives a quantitatively accurate description of the full restitution portrait measured from a bullfrog ventricle. The mapping can be derived as an asymptotic limit of an idealized ionic model in which a generalized concentration acts as a memory variable. This ionic basis clarifies how the present model differs from previous models. The ionic basis also provides the foundation for more extensive cardiac modeling: e.g., constructing a PDE model that may be used to study the effect of memory on propagation. The fitting procedure for the mapping is straightforward and can easily be applied to obtain a mathematical model for data from other experiments, including experiments on different species.
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http://dx.doi.org/10.1007/s11538-006-9116-6 | DOI Listing |
Neuroscience
January 2025
Chemistry Department (emeritus), Willamette University, Salem, OR, USA.
In two recent papers (Curr Trends Neurol 17: 83-98, 2023; J Neurophysiol 124: 1029-1044, 2020), James Lee has argued that his Transmembrane Electrostatically-Localized Cations (TELC) hypothesis offers a model of neuron transmembrane potentials that is superior to Hodgkin-Huxley classic cable theory and the Goldman-Hodgkin-Katz (GHK) equation. Here we examine critically the arguments in these papers, finding key weaknesses and fallacies. We also examine closely the literature cited by Lee, and find (i) strong support for the GHK equation; (ii) published measurements that contradict TELC predictions; and (iii) no convincing support for the TELC hypothesis.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
The Medical University of South Carolina, Charleston, SC, USA.
Background: Alzheimer's disease disproportionately affects women in the U.S., with two-thirds of individuals diagnosed being female.
View Article and Find Full Text PDFSci Rep
January 2025
School of Biological Sciences, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, 30332-0535, GA, USA.
Nat Commun
January 2025
Max Planck UCL Centre for Computational Psychiatry and Ageing Research, Max Planck Institute for Human Development, Berlin, Germany.
During memory formation, the hippocampus is presumed to represent the content of stimuli, but how it does so is unknown. Using computational modelling and human single-neuron recordings, we show that the more precisely hippocampal spiking variability tracks the composite features of each individual stimulus, the better those stimuli are later remembered. We propose that moment-to-moment spiking variability may provide a new window into how the hippocampus constructs memories from the building blocks of our sensory world.
View Article and Find Full Text PDFNat Commun
January 2025
Neurobiology Department, School of Biological Sciences, University of California, San Diego, CA, USA.
The hippocampal CA3 subregion is a densely connected recurrent circuit that supports memory by generating and storing sequential neuronal activity patterns that reflect recent experience. While theta phase precession is thought to be critical for generating sequential activity during memory encoding, the circuit mechanisms that support this computation across hippocampal subregions are unknown. By analyzing CA3 network activity in the absence of each of its theta-modulated external excitatory inputs, we show necessary and unique contributions of the dentate gyrus (DG) and the medial entorhinal cortex (MEC) to phase precession.
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