Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2013

Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning

Résumé

New neurons are continuously added to the dentate gyrus of the adult mammalian brain. During the critical period of a few weeks after birth when newborn neurons progressively mature, a restricted fraction is competitively selected to survive in an experience dependent manner, a condition for their contribution to memory processes. The mechanisms that control critical stages of experience-dependent functional incorporation of adult newborn neurons remain largely unknown. Here, we identify a unique tran-scriptional regulator of the functional integration of newborn neu-rons, the inducible immediate early gene zif268/egr1. We show that newborn neurons in zif268-KO mice undergo accelerated death during the critical period of 2-3 wk around their birth and exhibit deficient neurochemical and morphological maturation, including reduced GluR1 expression, increased NKCC1/KCC2b chloride cotransporter ratio, altered dendritic development, and marked spine growth defect. Investigating responsiveness of newborn neu-rons to activity-dependent expression of zif268 in learning, we demonstrate that in the absence of zif268, training in a spatial learning task during this critical period fails to recruit newborn neurons and promote their survival, leading to impaired long-term memory. This study reveals a previously unknown mechanism for the control of the selection, functional maturation, and experience-dependent recruitment of dentate gyrus newborn neurons that depends on the inducible immediate early gene zif268, processes that are critical for their contribution to hippocampal-dependent long-term memory.
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Dates et versions

hal-02396563 , version 1 (06-12-2019)

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Alexandra Veyrac, Alexandra Gros, Elodie Bruel-Jungerman, Christelle Rochefort, Félix Kleine Borgmann, et al.. Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110 (17), pp.7062-7067. ⟨10.1073/pnas.1220558110⟩. ⟨hal-02396563⟩
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