PT  - JOURNAL ARTICLE
AU  - Wenbin Wang
AU  - Song Lu
AU  - Tan Li
AU  - Yung-Wei Pan
AU  - Junhui Zou
AU  - Glen M. Abel
AU  - Lihong Xu
AU  - Daniel R. Storm
AU  - Zhengui Xia
TI  - Inducible Activation of ERK5 MAP Kinase Enhances Adult Neurogenesis in the Olfactory Bulb and Improves Olfactory Function
AID  - 10.1523/JNEUROSCI.3745-14.2015
DP  - 2015 May 20
TA  - The Journal of Neuroscience
PG  - 7833--7849
VI  - 35
IP  - 20
4099  - http://www.jneurosci.org/content/35/20/7833.short
4100  - http://www.jneurosci.org/content/35/20/7833.full
SO  - J. Neurosci.2015 May 20; 35
AB  - Recent discoveries have suggested that adult neurogenesis in the subventricular zone (SVZ) and olfactory bulb (OB) may be required for at least some forms of olfactory behavior in mice. However, it is unclear whether conditional and selective enhancement of adult neurogenesis by genetic approaches is sufficient to improve olfactory function under physiological conditions or after injury. Furthermore, specific signaling mechanisms regulating adult neurogenesis in the SVZ/OB are not fully defined. We previously reported that ERK5, a MAP kinase selectively expressed in the neurogenic regions of the adult brain, plays a critical role in adult neurogenesis in the SVZ/OB. Using a site-specific knock-in mouse model, we report here that inducible and targeted activation of the endogenous ERK5 in adult neural stem/progenitor cells enhances adult neurogenesis in the OB by increasing cell survival and neuronal differentiation. This conditional ERK5 activation also improves short-term olfactory memory and odor-cued associative olfactory learning under normal physiological conditions. Furthermore, these mice show enhanced recovery of olfactory function and have more adult-born neurons after a zinc sulfate-induced lesion of the main olfactory epithelium. We conclude that ERK5 MAP kinase is an important endogenous signaling pathway regulating adult neurogenesis in the SVZ/OB, and that conditional activation of endogenous ERK5 is sufficient to enhance adult neurogenesis in the OB thereby improving olfactory function both under normal conditions and after injury.