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在自闭症谱系障碍计算模型中,异常眨眼条件反射背后的皮质 - 小脑超连接和浦肯野细胞减少

Cortico-Cerebellar Hyper-Connections and Reduced Purkinje Cells Behind Abnormal Eyeblink Conditioning in a Computational Model of Autism Spectrum Disorder.

作者信息

Trimarco Emiliano, Mirino Pierandrea, Caligiore Daniele

机构信息

Computational and Translational Neuroscience Laboratory, Institute of Cognitive Sciences and Technologies, National Research Council, Rome, Italy.

Laboratory of Neuropsychology of Visuo-Spatial and Navigational Disorders, Department of Psychology, "Sapienza" University, Rome, Italy.

出版信息

Front Syst Neurosci. 2021 Dec 17;15:666649. doi: 10.3389/fnsys.2021.666649. eCollection 2021.

Abstract

Empirical evidence suggests that children with autism spectrum disorder (ASD) show abnormal behavior during delay eyeblink conditioning. They show a higher conditioned response learning rate and earlier peak latency of the conditioned response signal. The neuronal mechanisms underlying this autistic behavioral phenotype are still unclear. Here, we use a physiologically constrained spiking neuron model of the cerebellar-cortical system to investigate which features are critical to explaining atypical learning in ASD. Significantly, the computer simulations run with the model suggest that the higher conditioned responses learning rate mainly depends on the reduced number of Purkinje cells. In contrast, the earlier peak latency mainly depends on the hyper-connections of the cerebellum with sensory and motor cortex. Notably, the model has been validated by reproducing the behavioral data collected from studies with real children. Overall, this article is a starting point to understanding the link between the behavioral and neurobiological basis in ASD learning. At the end of the paper, we discuss how this knowledge could be critical for devising new treatments.

摘要

实证证据表明,患有自闭症谱系障碍(ASD)的儿童在延迟眨眼条件反射过程中表现出异常行为。他们表现出更高的条件反应学习率和条件反应信号的更早峰值潜伏期。这种自闭症行为表型背后的神经元机制仍不清楚。在这里,我们使用小脑 - 皮质系统的生理约束脉冲神经元模型来研究哪些特征对于解释ASD中的非典型学习至关重要。值得注意的是,用该模型进行的计算机模拟表明,较高的条件反应学习率主要取决于浦肯野细胞数量的减少。相比之下,更早的峰值潜伏期主要取决于小脑与感觉和运动皮层的过度连接。值得注意的是,该模型通过再现从对真实儿童的研究中收集的行为数据得到了验证。总体而言,本文是理解ASD学习中行为与神经生物学基础之间联系的起点。在论文结尾,我们讨论了这些知识对于设计新疗法可能有多重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55fc/8719301/e4e7df415403/fnsys-15-666649-g0001.jpg

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