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

Alexandra Veyrac*, Alexandra Gros, Elodie Bruel-Jungerman, Christelle Rochefort, Felix B. Kleine Borgmann, Sebastian Jessberger, Serge Laroche

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

63 Citations (Scopus)

Abstract

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 neurons, 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-ronsto activity-dependent expressionofzif268inlearning,wedem-onstrate 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.

Original languageEnglish
Pages (from-to)7062-7067
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number17
DOIs
Publication statusPublished - 23 Apr 2013
Externally publishedYes

Keywords

  • Hippocampus
  • Memory consolidation
  • Neurogenesis
  • Plasticity
  • Transcription factor

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