纽约大学Dora E. Angelaki团队近日取得一项新成果。经过不懈努力，他们揭示了自闭症小鼠模型中常见的计算和神经异常。2025年6月3日出版的《自然—神经科学》发表了这项成果。

在这里，该研究组利用高产量的啮齿动物心理物理学，广泛的行为建模和全脑单细胞细胞外记录来评估与ASD相关的不同遗传扰动的小鼠是否表现出相同的计算异常，如果是这样，那么不同基因型的神经生理特征是共享的。携带Fmr1、Cntnap2或Shank3B突变的小鼠在决策过程中表现出迟钝的先验更新。与灵活更新先验的小鼠相比，不灵活更新先验与先验编码权重从感觉皮层向额叶皮层的转移有关。

此外，无主题ASD模型的额叶区域显示出更多的编码单元偏离动物的长期先验，并且感觉反应无法区分预期和意外的观察结果。这些发现表明ASD的不同遗传实例可能产生共同的神经生理和行为表型。

据介绍，计算精神病学研究表明，患有自闭症谱系障碍（ASD）的个体会僵化地更新他们的期望。

附：英文原文

Title: A common computational and neural anomaly across mouse models of autism

Author: Noel, Jean-Paul, Balzani, Edoardo, Acerbi, Luigi, Benson, Julius, Savin, Cristina, Angelaki, Dora E.

Issue&Volume: 2025-06-03

Abstract: Computational psychiatry studies suggest that individuals with autism spectrum disorder (ASD) inflexibly update their expectations. Here we leveraged high-yield rodent psychophysics, extensive behavioral modeling and brain-wide single-cell extracellular recordings to assess whether mice with different genetic perturbations associated with ASD show this same computational anomaly, and if so, what neurophysiological features are shared across genotypes. Mice harboring mutations in Fmr1, Cntnap2 or Shank3B show a blunted update of priors during decision-making. Compared with mice that flexibly updated their priors, inflexible updating of priors was associated with a shift in the weighting of prior encoding from sensory to frontal cortices. Furthermore, frontal areas in mouse models of ASD showed more units encoding deviations from the animals’ long-run prior, and sensory responses did not differentiate between expected and unexpected observations. These findings suggest that distinct genetic instantiations of ASD may yield common neurophysiological and behavioral phenotypes.

DOI: 10.1038/s41593-025-01965-8

Source: https://www.nature.com/articles/s41593-025-01965-8