Circuit-level theories for sensory dysfunction in autism: convergence across mouse models.
Circuit-level theories for sensory dysfunction in autism: convergence across mouse models.
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DOI：
10.3389/fneur.2023.1254297
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发表时间：
2023
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
自闭症谱系障碍（ASD）患者表现出一系列不同的行为特征和遗传背景，但不同遗传形式的自闭症是否涉及脑功能的趋同病理生理尚不清楚。在此，我们分析了多个转基因ASD小鼠模型中神经回路功能趋同缺陷的证据。我们关注的是新皮质的感觉区域，那里的电路差异可能是非典型感觉处理的基础，这是自闭症的一个主要特征。已经提出了许多不同的ASD回路水平理论，包括兴奋抑制（E-I）比例增加和高兴奋性、小白蛋白（PV）中间神经元回路功能低下、稳态可塑性受损、感觉编码退化等。我们回顾了这些理论，并评估了每种ASD小鼠模型的趋同程度。在行为上，我们的分析表明，在许多ASD模型中，先天的感官检测行为增强，感官辨别行为受损。神经生理上，PV功能减退和E-I比值升高普遍存在，但很少产生高兴奋性和过度尖峰。相反，感觉调节和神经编码的其他方面通常会退化，这可能解释了辨别行为受损的原因。两种截然不同的表型簇具有相反的神经回路特征在小鼠模型中是明显的。这样的聚类可以提示自闭症的生理亚型，这可能有助于定制治疗方法的发展。
Individuals with autism spectrum disorder (ASD) exhibit a diverse range of behavioral features and genetic backgrounds, but whether different genetic forms of autism involve convergent pathophysiology of brain function is unknown. Here, we analyze evidence for convergent deficits in neural circuit function across multiple transgenic mouse models of ASD. We focus on sensory areas of neocortex, where circuit differences may underlie atypical sensory processing, a central feature of autism. Many distinct circuit-level theories for ASD have been proposed, including increased excitation–inhibition (E–I) ratio and hyperexcitability, hypofunction of parvalbumin (PV) interneuron circuits, impaired homeostatic plasticity, degraded sensory coding, and others. We review these theories and assess the degree of convergence across ASD mouse models for each. Behaviorally, our analysis reveals that innate sensory detection behavior is heightened and sensory discrimination behavior is impaired across many ASD models. Neurophysiologically, PV hypofunction and increased E–I ratio are prevalent but only rarely generate hyperexcitability and excess spiking. Instead, sensory tuning and other aspects of neural coding are commonly degraded and may explain impaired discrimination behavior. Two distinct phenotypic clusters with opposing neural circuit signatures are evident across mouse models. Such clustering could suggest physiological subtypes of autism, which may facilitate the development of tailored therapeutic approaches.
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影响因子：
3.7
作者：
Ariza, Jeanelle;Rogers, Haille;Martinez-Cerdeno, Veronica
通讯作者：
Martinez-Cerdeno, Veronica
影响因子：
6.1
作者：
Balasco, Luigi;Pagani, Marco;Bozzi, Yuri
通讯作者：
Bozzi, Yuri
影响因子：
10.5
作者：
Boltor, Patrick F.;Carcani-Rathwell, Iris;Rutter, Michael
通讯作者：
Rutter, Michael
DOI：
10.1523/jneurosci.3077-12.2012
发表时间：
2012-09-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Blackman MP;Djukic B;Nelson SB;Turrigiano GG
通讯作者：
Turrigiano GG
影响因子：
2.5
作者：
Blakemore, Sarah-Jayne;Tavassoli, Teresa;Haggard, Patrick
通讯作者：
Haggard, Patrick