Architectural organization of ∼1,500-neuron modular minicolumnar disinhibitory circuits in healthy and Alzheimer's cortices.
Architectural organization of ∼1,500-neuron modular minicolumnar disinhibitory circuits in healthy and Alzheimer's cortices.
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DOI：
10.1016/j.celrep.2023.112904
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发表时间：
2023-07
期刊：
影响因子：
8.8
通讯作者：
J. J. Zhu-J.
中科院分区：
文献类型：
--
作者：
J. J. Zhu-J.
神经元回路结构的获取是理解大脑功能和功能障碍的核心，仍然具有极大的挑战性。在这里，我报告的发展，同时和顺序octuplesexdecuple全细胞膜片钳记录系统，使建筑重建复杂的皮层电路。该方法揭示了典型的第1层单花束细胞（SBC）导致的去抑制神经元回路在小鼠体感，运动，前额叶和内侧内嗅皮质。1,500美元的神经元模块化电路具有跨层、单向、微柱和独立的去抑制功能，并优化了皮层的复杂性、微妙性、可塑性、变异性和冗余性。此外，建筑重建揭示了年龄依赖性赤字的SBC-去抑制突触在加速老化的小鼠倾向8，阿尔茨海默氏病的动物模型。这些缺陷表现出阿尔茨海默氏症样皮质扩散的特征以及与认知障碍的相关性。这些发现解密的基本处理单元在健康和阿尔茨海默氏症的小鼠皮层的操作，并验证了八三零零膜片钳记录的复杂神经元电路的建筑重建的功效。
Acquisition of neuronal circuit architectures, central to understanding brain function and dysfunction, remains prohibitively challenging. Here I report the development of a simultaneous and sequential octuplesexdecuple whole-cell patch-clamp recording system that enables architectural reconstruction of complex cortical circuits. The method unveils the canonical layer 1 single bouquet cell (SBC)-led disinhibitory neuronal circuits across the mouse somatosensory, motor, prefrontal, and medial entorhinal cortices. The $1,500-neuron modular circuits feature the translaminar, unidirectional, minicolumnar, and independent disinhibition and optimize cortical complexity, subtlety, plasticity, variation, and redundancy. Moreover, architectural reconstruction uncovers age-dependent deficits at SBC-disinhibited synapses in the senescence-accelerated mouse prone 8, an animal model of Alzheimer’s disease. The deficits exhibit the characteristic Alzheimer’s-like cortical spread and correlation with cognitive impairments. These findings decrypt operations of the elementary processing units in healthy and Alzheimer’s mouse cortices and validate the efficacy of octuple-sexdecuple patch-clamp recordings for architectural reconstruction of complex neuronal circuits.