Biology subjects

Lupascu, C. A.

Publications and source records attributed to Lupascu, C. A..

3 recordsLinked to original sources

bioRxiv2026

Functionally convergent but parametrically distinct solutions: Robust degeneracy in a population of computational models of early-birth rat CA1 pyramidal neurons

BackgroundFlexibility and robustness of neuronal function are closely linked to degeneracy, the ability of distinct structural or parametric configurations to produce similar functional outcomes. At the cellular level, this often manifests as ion-channel degeneracy, in which multiple combinations of intrinsic conductances yield comparable electrophysiological phenotypes. MethodologyWe used a population-based, data-driven modelling framework to generate large ensembles of biophysically detailed CA1 pyramidal neuron models constrained by somatic electrophysiological features extracted from patch-clamp recordings in acute slices from early-birth rats. 10 reconstructed morphologies were incorporated, and model populations were analyzed using parameter correlation analysis, principal component analysis, and generalization tests to assess robustness, degeneracy, and morphology dependence of intrinsic properties. ConclusionsAcross the model population, similar somatic firing behaviours emerged from widely different combinations of intrinsic parameters, demonstrating robust two-level ion channel degeneracy both within and across morphologies. Each morphology occupied a distinct region of parameter space, indicating morphology-specific compensatory effects, while weak pairwise parameter correlations suggested distributed compensation rather than tight parameter dependencies. Even with a fixed morphology, multiple parameter subspaces supported comparable electrophysiological phenotypes. Generalization across morphologies was structure-dependent and non-reciprocal, with successful parameter similarity occurring preferentially between structurally similar neurons. Interestingly, to accurately simulate spike-frequency adaptation, it was important to retain some kinetic properties of the ion channel models as free parameters during optimization. Together, these findings show that dendrite morphology shapes the valid parameter space, and similar electrophysiology of CA1 pyramidal neurons arises from the interplay between structural variability and ion-channel diversity. This work highlights the importance of population-based modelling for capturing biological variability and provides insights into how neuronal robustness might be maintained despite substantial heterogeneity, and offers a scalable pipeline for generating biophysically realistic CA1 neuron populations for use in network simulations. Author summaryNeurons must reliably process information even though their internal components, such as ion channels and cellular shape, can vary widely from cell to cell. How stable behaviour emerges from such variability is a fundamental question in neuroscience. In this study, we explored this problem using detailed computer models of early-birth rat hippocampal CA1 pyramidal neurons, a cell type that plays a central role in learning and memory. Instead of building a single "average" neuron model, we created large populations of models that all reproduced key experimental recordings but differed in their internal parameters. We found that neurons with different shapes and different combinations of ion channels could nevertheless generate similar electrical activity. This phenomenon, known as ion channel degeneracy, allows neurons to remain functional despite biological variability or perturbations. Our results show that neuronal shape strongly influences which parameter combinations are viable, but that multiple solutions exist even for the same morphology. The population of models we provide offers a resource for future studies of early-birth CA1 pyramidal cell function and dysfunction.

neuroscience↗

bioRxiv2023

Community-based Reconstruction and Simulation of a Full-scale Model of Region CA1 of Rat Hippocampus

The CA1 region of the hippocampus is one of the most studied regions of the rodent brain, thought to play an important role in cognitive functions such as memory and spatial navigation. Despite a wealth of experimental data on its structure and function, it has been challenging to reconcile information obtained from diverse experimental approaches. To address this challenge, we present a community-driven, full-scale in silico model of the rat CA1 that integrates a broad range of experimental data, from synapse to network, including the reconstruction of its principal afferents, the Schaffer collaterals, and a model of the effects that acetylcholine has on the system. We tested and validated each model component and the final network model, and made input data, assumptions, and strategies explicit and transparent. The unique flexibility of the model allows scientists to address a range of scientific questions. In this article, we describe the methods used to set up simulations that reproduce and extend in vitro and in vivo experiments. Among several applications in the article, we focus on theta rhythm, a prominent hippocampal oscillation associated with various behavioral correlates and use our computer model to reproduce and reconcile experimental findings. Finally, we make data, code and model available through the hippocampushub.eu portal, which also provides an extensive set of analyses of the model and a user-friendly interface to facilitate adoption and usage. This neuroscience community-driven model represents a valuable tool for integrating diverse experimental data and provides a foundation for further research into the complex workings of the hippocampal CA1 region.

neuroscience↗

bioRxiv2020

Systematic comparison and automated validation of detailed models of hippocampal neurons

Anatomically and biophysically detailed data-driven neuronal models have become widely used tools for understanding and predicting the behavior and function of neurons. Due to the increasing availability of experimental data from anatomical and electrophysiological measurements as well as the growing number of computational and software tools that enable accurate neuronal modeling, there are now a large number of different models of many cell types available in the literature. These models were usually built to capture a few important or interesting properties of the given neuron type, and it is often unknown how they would behave outside their original context. In addition, there is currently no simple way of quantitatively comparing different models regarding how closely they match specific experimental observations. This limits the evaluation, re-use and further development of the existing models. Further, the development of new models could also be significantly facilitated by the ability to rapidly test the behavior of model candidates against the relevant collection of experimental data. We address these problems for the representative case of the CA1 pyramidal cell of the rat hippocampus by developing an open-source Python test suite, which makes it possible to automatically and systematically test multiple properties of models by making quantitative comparisons between the models and electrophysiological data. The tests cover various aspects of somatic behavior, and signal propagation and integration in apical dendrites. To demonstrate the utility of our approach, we applied our tests to compare the behavior of several different hippocampal CA1 pyramidal cell models from the ModelDB database against electrophysiological data available in the literature, and concluded that each of these models provides a good match to experimental results in some domains but not in others. We also show how we employed the test suite to aid the development of models within the European Human Brain Project (HBP), and describe the integration of the tests into the validation framework developed in the HBP, with the aim of facilitating more reproducible and transparent model building in the neuroscience community. Author summary Anatomically and biophysically detailed neuronal models are useful tools in neuroscience because they allow the prediction of the behavior and the function of the studied cell type under circumstances that are hard to investigate experimentally. However, most detailed biophysical models have been built to capture a few selected properties of the real neuron, and it is often unknown how they would behave under different circumstances, or whether they can be used to successfully answer different scientific questions. To help the modeling community develop better neural models, and make the process of model building more reproducible and transparent, we developed a test suite that enables the comparison of the behavior of models of neurons in the rat hippocampus and their evaluation against experimental data. Applying our tests to several models available in the literature, we show that each model is able to capture some of the important properties of the real neuron but fails to match experimental data in other domains. We also use the test suite in the model development workflow of the European Human Brain Project to aid the construction of better models of hippocampal neurons and networks.

neuroscience↗