Kostovic I, Judas M, Kostovic-Knezevic L, Simic G, Delalle I, Chudy D, Sajin B, Petanjek Z
Department of Anatomy, School of Medicine, University of Zagreb, Republic of Croatia, Yugoslavia.
Int J Dev Biol. 1991 Sep;35(3):215-30.
The aim of this paper was to offer for the first time a selective and systematic description of the "Zabreb Neuroembryological Collection" of human brains and to illustrate the major results of our research team. Throughout these 16 years of continuous and systematic research, we have applied different techniques for demonstrating the cytoarchitectonics (Nissl staining), neuronal morphology (Golgi impregnation), synaptogenesis (EM analysis), growing pathways (acetylcholinesterase histochemistry) and transmitter-related properties of developing neuronal populations (immunocytochemistry and acetylcholinesterase histochemistry) on several hundred human brains ranging in age from the 5th week post-conception to 90 years. The combination of classical and modern research techniques applied to the constantly growing developmental collection, as well as the continuous evaluation of our data in the light of experimental work in non-human primates, has led to the discovery of an early synaptogenesis within the human cortical anlage and hitherto undescribed transient subplate zone; our results also provided the first comprehensive evidence concerning the timing and pattern of development of afferent fiber systems in the human cortex. All this enabled us to offer a well-documented and coherent reconstruction of major histogenetic events in the human brain. We concluded that structural remodeling and reorganization of the brain, from the transient patterns of the fetal organization through the postnatal phase of transient overproduction of circuitry elements to the final maturation, is the crucial principle of development. Fetal neuronal elements (afferents, synapses and postsynaptic neurons) display transient patterns of laminar, vertical and modular organization and transient cellular interactions and competition in the subplate zone are crucial for the formation of cortical connections. The elucidation of the nature and timing of these histogenetic reorganizational events in the human brain represents the first step towards determining the neurobiological basis of the emergence of behavior, neural functions and cognition in human fetuses, infants and children, which takes place during perinatal and early postnatal life.
本文旨在首次对人类大脑的“萨格勒布神经胚胎学藏品”进行选择性和系统性描述，并阐述我们研究团队的主要研究成果。在这连续16年的系统性研究中，我们运用了不同技术，对数百例年龄从受孕后第5周直至90岁的人类大脑进行细胞构筑学（尼氏染色）、神经元形态学（高尔基浸染）、突触发生（电镜分析）、生长通路（乙酰胆碱酯酶组织化学）以及发育中神经元群体的递质相关特性（免疫细胞化学和乙酰胆碱酯酶组织化学）的研究。将经典与现代研究技术应用于持续增长的发育学藏品，并依据对非人灵长类动物的实验工作不断评估我们的数据，这使得我们发现了人类皮质原基内的早期突触发生以及迄今未被描述的短暂性板下层区域；我们的研究结果还首次提供了关于人类皮质传入纤维系统发育时间和模式的全面证据。所有这些使我们能够对人类大脑主要组织发生事件进行有充分文献记载且连贯一致的重建。我们得出结论，大脑的结构重塑和重组，从胎儿期组织的短暂模式，历经产后电路元件短暂过度生成阶段直至最终成熟，是发育的关键原则。胎儿神经元成分（传入神经、突触和突触后神经元）呈现出分层、垂直和模块化组织的短暂模式，并且板下层区域短暂的细胞相互作用和竞争对于皮质连接的形成至关重要。阐明人类大脑中这些组织发生重组事件的性质和时间，是确定人类胎儿、婴儿和儿童在围产期和产后早期出现行为、神经功能和认知的神经生物学基础的第一步。
