Zdravko Petanjek
Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Croatia
The major mechanism for generating diversity of neuronal connections beyond their genetic determination is the selective stabilization of the supernumerary synapses that had been proposed more than four decades ago. Selective stabilization assumes that during a period of overproduction of synapses, neuronal activity tunes the molecular structure of individual synapses and determines which ones will be removed from the network. The selective stabilization hypothesis gains support by the discovery that synaptic connections in the cerebral cortex of human and non-human primates are initially overproduced about twice in number and are pruned during puberty to reach the adult level at the onset of adolescence. However, recent brain imaging studies show the functional, structural and molecular maturation of connections, including their regression, might continue through adolescence and young adulthood, but direct cellular evidence is lacking. We provide the first evidence that developmental remodeling of dendritic synaptic spines on identified pyramidal neurons in the human prefrontal neocortex, including their transient overproduction and selective elimination, passes beyond the period of adolescence and continues throughout the third decade of life, before stabilizing to the adult level. This strongly supports the view that protracted cognitive and emotional development observed at that age depends predominantly on structural network reorganization, including elimination of supernumerary synapses and, not only on fine molecular tuning of stable neuronal connections. Those findings have implications for delineating the critical period and understanding the mechanisms of environmental impacts such as education and training on development of human cognitive capacities, and also, provide insight into the pathogenesis of late onset, human-specific, neuropsychiatric disorders.
Keywords: associative cortex, cortico-cortical connections, principal neurons, working memory, human specific psychology, schizophrenia, emerging adulthood