Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory.

Published

Journal Article

Although there is evidence suggesting that adult neurogenesis may contribute to hippocampus-dependent memory, signaling mechanisms responsible for adult hippocampal neurogenesis are not well characterized. Here we report that ERK5 mitogen-activated protein kinase is specifically expressed in the neurogenic regions of the adult mouse brain. The inducible and conditional knock-out (icKO) of erk5 specifically in neural progenitors of the adult mouse brain attenuated adult hippocampal neurogenesis. It also caused deficits in several forms of hippocampus-dependent memory, including contextual fear conditioning generated by a weak footshock. The ERK5 icKO mice were also deficient in contextual fear extinction and reversal of Morris water maze spatial learning and memory, suggesting that adult neurogenesis plays an important role in hippocampus-dependent learning flexibility. Furthermore, our data suggest a critical role for ERK5-mediated adult neurogenesis in pattern separation, a form of dentate gyrus-dependent spatial learning and memory. Moreover, ERK5 icKO mice have no memory 21 d after training in the passive avoidance test, suggesting a pivotal role for adult hippocampal neurogenesis in the expression of remote memory. Together, our results implicate ERK5 as a novel signaling molecule regulating adult neurogenesis and provide strong evidence that adult neurogenesis is critical for several forms of hippocampus-dependent memory formation, including fear extinction, and for the expression of remote memory.

Full Text

Duke Authors

Cited Authors

  • Pan, Y-W; Chan, GCK; Kuo, CT; Storm, DR; Xia, Z

Published Date

  • May 9, 2012

Published In

Volume / Issue

  • 32 / 19

Start / End Page

  • 6444 - 6455

PubMed ID

  • 22573667

Pubmed Central ID

  • 22573667

Electronic International Standard Serial Number (EISSN)

  • 1529-2401

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.6076-11.2012

Language

  • eng

Conference Location

  • United States