Quantitative prediction of intracellular dynamics and synaptic currents in a small neural circuit.

IF 2.3 4区 医学 Q2 MATHEMATICAL & COMPUTATIONAL BIOLOGY
Frontiers in Computational Neuroscience Pub Date : 2025-09-01 eCollection Date: 2025-01-01 DOI:10.3389/fncom.2025.1515194
Thiago B Burghi, Kyra Schapiro, Maria Ivanova, Huaxinyu Wang, Eve Marder, Timothy O'Leary
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引用次数: 0

Abstract

Fitting models to experimental intracellular data is challenging. While detailed conductance-based models are difficult to train, phenomenological statistical models often fail to capture the rich intrinsic dynamics of circuits such as central pattern generators (CPGs). A recent trend has been to employ tools from deep learning to obtain data-driven models that can quantitatively learn intracellular dynamics from experimental data. This paper addresses the general questions of modeling, training, and interpreting a large class of such models in the context of estimating the dynamics of a neural circuit. In particular, we use recently introduced Recurrent Mechanistic Models to predict the dynamics of a Half-Center Oscillator (HCO), a type of CPG. We construct the HCO by interconnecting two neurons in the Stomatogastric Ganglion using the dynamic clamp experimental protocol. This allows us to gather ground truth synaptic currents, which the model is able to predict-even though these currents are not used during training. We empirically assess the speed and performance of the training methods of teacher forcing, multiple shooting, and generalized teacher forcing, which we present in a unified fashion tailored to data-driven models with explicit membrane voltage variables. From a theoretical perspective, we show that a key contraction condition in data-driven dynamics guarantees the applicability of these training methods. We also show that this condition enables the derivation of data-driven frequency-dependent conductances, making it possible to infer the excitability profile of a real neuronal circuit using a trained model.

小神经回路中细胞内动力学和突触电流的定量预测。
将模型拟合到实验细胞内数据是具有挑战性的。虽然基于电导的详细模型很难训练,但现象学统计模型往往无法捕捉到诸如中央模式发生器(cpg)等电路的丰富内在动态。最近的一个趋势是使用深度学习的工具来获得数据驱动的模型,这些模型可以从实验数据中定量地学习细胞内动力学。本文在估计神经回路动态的背景下,解决了建模、训练和解释一类这样的模型的一般问题。特别地,我们使用最近引入的循环机制模型来预测半中心振荡器(HCO)的动力学,这是一种CPG。我们采用动态钳形实验方案,将口胃神经节的两个神经元相互连接,构建了HCO。这使我们能够收集到真实的突触电流,而模型能够预测这些电流——即使这些电流在训练过程中没有使用。我们通过经验评估了教师强迫、多次射击和广义教师强迫的训练方法的速度和性能,我们以统一的方式呈现了具有显式膜电压变量的数据驱动模型。从理论的角度来看,我们证明了数据驱动动力学中的一个关键收缩条件保证了这些训练方法的适用性。我们还表明,这种条件能够推导出数据驱动的频率相关电导,从而可以使用经过训练的模型推断出真实神经元电路的兴奋性。
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来源期刊
Frontiers in Computational Neuroscience
Frontiers in Computational Neuroscience MATHEMATICAL & COMPUTATIONAL BIOLOGY-NEUROSCIENCES
CiteScore
5.30
自引率
3.10%
发文量
166
审稿时长
6-12 weeks
期刊介绍: Frontiers in Computational Neuroscience is a first-tier electronic journal devoted to promoting theoretical modeling of brain function and fostering interdisciplinary interactions between theoretical and experimental neuroscience. Progress in understanding the amazing capabilities of the brain is still limited, and we believe that it will only come with deep theoretical thinking and mutually stimulating cooperation between different disciplines and approaches. We therefore invite original contributions on a wide range of topics that present the fruits of such cooperation, or provide stimuli for future alliances. We aim to provide an interactive forum for cutting-edge theoretical studies of the nervous system, and for promulgating the best theoretical research to the broader neuroscience community. Models of all styles and at all levels are welcome, from biophysically motivated realistic simulations of neurons and synapses to high-level abstract models of inference and decision making. While the journal is primarily focused on theoretically based and driven research, we welcome experimental studies that validate and test theoretical conclusions. Also: comp neuro
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