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分解线性动力系统(dLDS)模型揭示了秀丽隐杆线虫中瞬时的、上下文相关的动态连接性。

Decomposed Linear Dynamical Systems (dLDS) models reveal instantaneous, context-dependent dynamic connectivity in C. elegans.

作者信息

Yezerets Eva, Mudrik Noga, Charles Adam S

机构信息

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.

Center for Imaging Science, Johns Hopkins University, Baltimore, MD, 21218, USA.

出版信息

Commun Biol. 2025 Aug 13;8(1):1218. doi: 10.1038/s42003-025-08599-3.

Abstract

Mounting evidence indicates that neural "tuning" can be highly variable within an individual across time and across individuals. Furthermore, modulatory effects can change the relationship between neurons as a function of behavioral or other conditions, meaning that the changes in activity (the derivative) may be as important as the activity itself. Current computational models cannot capture the nonstationarity and variability of neural coding, preventing the quantitative evaluation of these effects. We therefore present a novel approach to analyze these effects in a well-studied organisms, C. elegans, leveraging recent advances in dynamical systems modeling: decomposed Linear Dynamical Systems (dLDS). Our approach enables the discovery of multiple parallel neural processes on different timescales using a set of linear operators that can be recombined in different ratios. Our model identifies "dynamic connectivity", describing patterns of dynamic neural interactions in time. We use these patterns to identify instantaneous, contextually-dependent, hierarchical roles of neurons; discover the underlying variability of neural representations even under seemingly discrete behaviors; and learn an aligned latent space underlying multiple worms' activity. By analyzing individual worms and neurons, we found that (1) changes in interneuron connectivity mediate efficient task-switching and (2) changes in sensory neuron connectivity show a mechanism of adaptation.

摘要

越来越多的证据表明,神经“调谐”在个体内部随时间以及在个体之间可能存在高度变异性。此外,调节效应可以根据行为或其他条件改变神经元之间的关系,这意味着活动的变化(导数)可能与活动本身同样重要。当前的计算模型无法捕捉神经编码的非平稳性和变异性,从而阻碍了对这些效应的定量评估。因此,我们提出了一种新方法,利用动力系统建模的最新进展,在经过充分研究的线虫中分析这些效应:分解线性动力系统(dLDS)。我们的方法能够使用一组可以以不同比例重新组合的线性算子,在不同时间尺度上发现多个并行的神经过程。我们的模型识别出“动态连接性”,描述了随时间变化的动态神经相互作用模式。我们利用这些模式来识别神经元的瞬时、上下文相关的层次角色;即使在看似离散的行为下,也能发现神经表征的潜在变异性;并学习多个线虫活动背后的对齐潜在空间。通过分析单个线虫和神经元,我们发现:(1)中间神经元连接性的变化介导了高效的任务切换;(2)感觉神经元连接性的变化显示出一种适应机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b052/12350842/79a21e2bbbfc/42003_2025_8599_Fig1_HTML.jpg

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