Zagreb research collection of human brains for developmental neurobiologists and clinical neuroscientists.

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.