人类小脑中浦肯野细胞树突的非异速生长扩张和增强的分隔化
Non-allometric expansion and enhanced compartmentalization of Purkinje cell dendrites in the human cerebellum.
作者信息
Busch Silas E, Hansel Christian
机构信息
Department of Neurobiology and Neuroscience Institute, The University of Chicago, Chicago, IL, USA.
出版信息
bioRxiv. 2025 Feb 20:2024.09.09.612113. doi: 10.1101/2024.09.09.612113.
Purkinje cell (PC) dendrites are optimized to integrate the vast cerebellar input array and drive the sole cortical output. PCs are classically seen as stereotypical computational units, yet mouse PCs are morphologically diverse and those with multi-branched structure can receive non-canonical climbing fiber (CF) multi-innervation that confers independent compartment-specific signaling. While otherwise uncharacterized, human PCs are universally multi-branched. Do they exceed allometry to achieve enhanced integrative capacities relative to mouse PCs? To answer this, we used several comparative histology techniques in adult human and mouse to analyze cellular morphology, parallel fiber (PF) and CF input arrangement, and regional PC demographics. Human PCs are substantially larger than previously described; they exceed allometric constraint by cortical thickness and are the largest neuron in the brain with 6-7cm total dendritic length. Unlike mouse, human PC dendrites ramify horizontally to form a multi-compartment motif that we show can receive multiple CFs. Human spines are denser (6.9 vs 4.9 spines/μm), larger (~0.36 vs 0.29μm), and include an unreported 'spine cluster' structure-features that may be congruent with enhanced PF association and amplification as human-specific adaptations. By extrapolation, human PCs may receive 500,000 to 1 million synaptic inputs compared with 30-40,000 in mouse. Collectively, human PC morphology and input arrangement is quantitatively and qualitatively distinct from rodent. Multi-branched PCs are more prevalent in posterior and lateral cerebellum, co-varying with functional boundaries, supporting the hypothesis that this morphological motif permits expanded input multiplexing and may subserve task-dependent needs for input association.
浦肯野细胞(PC)的树突经过优化,以整合大量的小脑输入阵列并驱动唯一的皮质输出。传统上,PC被视为刻板的计算单元,但小鼠的PC在形态上具有多样性,那些具有多分支结构的PC可以接受非典型的攀缘纤维(CF)多神经支配,从而赋予独立的隔室特异性信号传导。虽然人类PC的其他特征尚未明确,但它们普遍具有多分支结构。相对于小鼠PC,它们是否超越了异速生长规律以实现增强的整合能力?为了回答这个问题,我们在成年人类和小鼠中使用了几种比较组织学技术,以分析细胞形态、平行纤维(PF)和CF输入排列以及区域PC的统计数据。人类PC比先前描述的要大得多;它们超出了皮质厚度的异速生长限制,是大脑中最大的神经元,总树突长度为6-7厘米。与小鼠不同,人类PC的树突水平分支形成多隔室模式,我们发现这种模式可以接受多个CF。人类的棘突更密集(6.9个/μm对4.9个/μm)、更大(约0.36μm对0.29μm),并且包括一种未报道的“棘突簇”结构特征,这些特征可能与作为人类特异性适应的增强的PF关联和放大相一致。据推断,人类PC可能接受500,000至100万个突触输入,而小鼠为30,000至40,000个。总体而言,人类PC形态和输入排列在数量和质量上与啮齿动物不同。多分支PC在后小脑和外侧小脑中更为普遍,与功能边界共同变化,支持了这种形态模式允许扩展输入复用并可能满足任务依赖的输入关联需求的假设。