Referenced in: none

Automatically associated channels: Kir6.2

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

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

Journal, date & volume: Proc. Natl. Acad. Sci. U.S.A., 2013 Apr 23 , 110, 7062-7

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23569253

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 transcriptional 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 neurons 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.