School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA.
Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA.
Exp Physiol. 2024 Jan;109(1):55-65. doi: 10.1113/EP091099. Epub 2023 Mar 26.
Muscle spindles encode mechanosensory information by mechanisms that remain only partially understood. Their complexity is expressed in mounting evidence of various molecular mechanisms that play essential roles in muscle mechanics, mechanotransduction and intrinsic modulation of muscle spindle firing behaviour. Biophysical modelling provides a tractable approach to achieve more comprehensive mechanistic understanding of such complex systems that would be difficult/impossible by more traditional, reductionist means. Our objective here was to construct the first integrative biophysical model of muscle spindle firing. We leveraged current knowledge of muscle spindle neuroanatomy and in vivo electrophysiology to develop and validate a biophysical model that reproduces key in vivo muscle spindle encoding characteristics. Crucially, to our knowledge, this is the first computational model of mammalian muscle spindle that integrates the asymmetric distribution of known voltage-gated ion channels (VGCs) with neuronal architecture to generate realistic firing profiles, both of which seem likely to be of great biophysical importance. Results predict that particular features of neuronal architecture regulate specific characteristics of Ia encoding. Computational simulations also predict that the asymmetric distribution and ratios of VGCs is a complementary and, in some instances, orthogonal means to regulate Ia encoding. These results generate testable hypotheses and highlight the integral role of peripheral neuronal structure and ion channel composition and distribution in somatosensory signalling.
肌梭通过部分尚未完全了解的机制来编码机械感觉信息。越来越多的证据表明,各种分子机制在肌肉力学、机械转导和肌梭放电行为的固有调制中发挥着重要作用,这充分体现了肌梭的复杂性。生物物理建模为实现对这些复杂系统更全面的机制理解提供了一种可行的方法,而这通过更传统的、简化论的方法是很难(甚至不可能)实现的。我们的目标是构建第一个肌梭放电的综合生物物理模型。我们利用肌梭神经解剖学和体内电生理学的现有知识,开发并验证了一个能够再现体内肌梭关键编码特征的生物物理模型。至关重要的是,据我们所知,这是第一个整合了已知电压门控离子通道(VGC)的不对称分布和神经元结构的哺乳动物肌梭计算模型,以产生现实的放电模式,这两者似乎都具有重要的生物物理意义。研究结果表明,神经元结构的特定特征调节 Ia 编码的特定特征。计算模拟还表明,VGC 的不对称分布和比例是调节 Ia 编码的一种补充且在某些情况下是正交的手段。这些结果产生了可测试的假设,并强调了外周神经元结构和离子通道组成和分布在躯体感觉信号中的整体作用。