The birth of new neurons (neurogenesis) does not end completely during development but continues throughout all life in two areas of the adult nervous system, i.e. subventricular zone and hippocampus. Recent research has shown that hippocampal neurogenesis is crucial for memory formation. These studies, however, have not yet clarified how the newborn neurons are integrated in the existing circuits and thus contribute to new memories formation and to the maintenance of old ones.
The team of researchers of CNR-LUMSA-EBRI at the European Centre for Brain Research, organization established in Rome with the key contribution of the Santa Lucia Foundation, has taken a step forward to understand the requirements of newborn neurons in the process of learning and memory. The neuroscientists coordinated by dr. Felice Tirone of the Institute of Neurobiology and Molecular Medicine (INMM) of CNR, in collaboration with prof. Vincenzo Cestari of the Institute for Neuroscience of CNR and the LUMSA University and with dr. Alberto Bacci of the European Brain Research Institute, have shown that a key factor for neurogenesis is represented by the speed of differentiation of progenitors (stem cells that give rise to neurons) in hippocampus. From such speed will in fact depend the success of the whole process. “New neurons must maturate according to a correct temporal sequence in order to become able to acquire new memories and retrieve the existing ones”, explains Tirone.
This study is based on a new experimental approach, that involves the generation of a mice line in which the differentiation of newborn neurons is accelerated without altering their number. This is obtained by the selective expression in neural progenitors of the hippocampus of PC3/Tis21, a gene specifically able to accelerate the differentiation of these and other types of neural progenitors.
“Compelling new neurons to rush ahead in their differentiation for a predefined time period, we have observed that a small number of neurons of 2-3 weeks of age is critical for learning,” continues the INMM-CNR researcher. “In fact, mice so treated are not only unable to learn new spatial information, but they are also unable to use previously acquired memories.”
“PC3/Tis21, of which we have previously observed an action against brain tumors in consequence of its ability to promote differentiation of neural progenitor cells, might indeed have other practical outcomes” continues Tirone “since it is activated by Nerve Growth Factor, a molecule whose deprivation appears to be an important component of Alzheimer’s disease. In fact hippocampus is one of the first brain regions damaged by Alzheimer’s disease, which is characterized mainly by temporal and spatial disorientation and by a memory deficit. We might gain some useful information also to understand the mechanisms underlying this disease.”
Thus, it is an open and relevant question in neuroscience the understanding of mechanisms and factors that control or influence adult neurogenesis, in the field of memory as these researches now indicate, but also of depression, which, as some researchers have suggested, might take place in consequence of a defective adult neurogenesis.
- Farioli-Vecchioli et al. The Timing of Differentiation of Adult Hippocampal Neurons Is Crucial for Spatial Memory. PLoS Biology, 2008; 6 (10): e246 DOI: 10.1371/journal.pbio.0060246
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