Cell death promotes learning growth

Background. The hippocampal formation has long been associated with the execution of higher-order cognitive functions, and impairment of this structure following severe stress and aging has been linked to cognitive disturbances. In order to understand the involvement of the hippocampal formation in the mediation of normal and pathological behaviors, much attention has recently been devoted to hippocampal neurogenesis. The dentate gyrus of the hippocampal formation has the ability to generate new neurons throughout the entire life. Surviving de novo produced cells develop into granule neurons and integrate into the functional circuitry. Neurogenesis has been proposed to play a role in hippocampal-mediated learning and has been implicated in the appearance of behavioral pathologies associated with the hippocampal formation.

Aim of the work. Although evidence suggest that neurogenesis play a role in spatial learning, the effect of learning on cell proliferation remains unclear. The authors generated and tested the hypothesis that different phases of spatial learning measured in the Morris water maze have distinct actions on cell proliferation. In this task, two phases of learning can be distinguished: an early phase during which performance improves rapidly, and a late phase during which asymptotic levels of performance are reached. These two phases seem to involve different brain processes and consequently may differentially influence neurogenesis.

Results. The authors demonstrated that the late phase of learning has a multifaceted effect on neurogenesis depending on the birth date of new neurons. The number of newly born cells increased contingently with the late phase and a large proportion of these cells survived for at least 4 weeks and differentiated into neurons. In contrast, the late phase learning decreased the number of newly born cells produced during the early phase. This learning-induced decrease in the number of newly generated cells results most probably from the death of the cells. Strikingly, cell death and not proliferation was positively correlated with performance in the water-maze. Thus, rats with the lowest cell death were less able to acquire and use spatial information than those with the highest cell death.

Conclusion. The results reveal a complex modulation of learning on brain plasticity, which induces death and proliferation of different populations of cells. Most importantly, they introduce the notion that removing neurons from the adult brain can be an important process in learning and memory and a novel mechanism through which neurogenesis may influence normal and pathological behaviors.

Citation source: Molecular Psychiatry 2003 Volume 8, number 12, pages 974-982.

AUTHORS: Matè Daniel Döbrössy*, Elodie Drapeau*, Catherine Aurousseau, Michel Le Moal, Pier Vincenzo Piazza, Djoher Nora Abrous * have equally contributed to the work

INSERM U259, University of Bordeaux, Domaine de Carreire, Bordeaux, France

For further information on this work, please contact Dr. Nora Abrous, INSERM U.588, Institut François Magendie, Rue Camille Saint-Saëns, 33077 Bordeaux Cedex, France. Tel: 33-5-57-57-36-86, Fax: 33-5-56-96-68-93, E-mail: nora.abrous@bordeaux.inserm.fr

Molecular Psychiatry is published by the Nature Publishing Group. http://www.nature.com/mp

Editor: Julio Licinio, M.D.; phone: 310-825-7113; FAX: 310-206-6715; e-mail: licinio@ucla.edu

For a copy of this article, please contact Aimee Midei, Editorial Assistant, e-mail: molecularpsychiatry@mednet.ucla.edu.

PLEASE CITE MOLECULAR PSYCHIATRY AS THE SOURCE OF THIS MATERIAL.

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