Genetic control of adult neurogenesis: interplay of differentiation, proliferation and survival modulates new neurons function, and memory circuits
- Institute of Cell Biology and Neurobiology, National Research Council, Fondazione Santa Lucia, Rome, Italy
Within the hippocampal circuitry, the basic function of the dentate gyrus is to transform the memory input coming from the enthorinal cortex into sparse and categorized outputs to CA3, in this way separating related memory information. New neurons generated in the dentate gyrus during adulthood appear to facilitate this process, allowing a better separation between closely spaced memories (pattern separation). The evidence underlying this model has been gathered essentially by ablating the newly adult-generated neurons. This approach, however, does not allow monitoring of the integration of new neurons into memory circuits and is likely to set in motion compensatory circuits, possibly leading to an underestimation of the role of new neurons. Here we review the background of the basic function of the hippocampus and of the known properties of new adult-generated neurons. In this context, we analyze the cognitive performance in mouse models generated by us and others, with modified expression of the genes Btg2 (PC3/Tis21), Btg1, Pten, BMP4, etc., where new neurons underwent a change in their differentiation rate or a partial decrease of their proliferation or survival rate rather than ablation. The effects of these modifications are equal or greater than full ablation, suggesting that the architecture of circuits, as it unfolds from the interaction between existing and new neurons, can have a greater functional impact than the sheer number of new neurons. We propose a model which attempts to measure and correlate the set of cellular changes in the process of neurogenesis with the memory function.
Keywords: adult neurogenesis, differentiation, proliferation, Btg1, Btg2, Tis21, hippocampus, memory
Citation: Tirone F, Farioli-Vecchioli S, Micheli L, Ceccarelli M and Leonardi L (2013) Genetic control of adult neurogenesis: interplay of differentiation, proliferation and survival modulates new neurons function, and memory circuits. Front. Cell. Neurosci. 7:59. doi: 10.3389/fncel.2013.00059
Received: 13 February 2013; Accepted: 15 April 2013;
Published online: 14 May 2013.
Edited by:Eran Meshorer, The Hebrew University of Jerusalem, Israel
Reviewed by:Mohamed Jaber, University of Poitiers, France
Jean-Claude Platel, University Joseph Fourrier, France
Hung-Ray, Korea University College of Medicine, South Korea
Copyright © 2013 Tirone, Farioli-Vecchioli, Micheli, Ceccarelli and Leonardi. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Felice Tirone, Institute of Cell Biology and Neurobiology, Consiglio Nazionale delle Ricerche, Fondazione S.Lucia, via del Fosso di Fiorano 64, 00143 Rome, Italy. e-mail: firstname.lastname@example.org