title: Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity.
abstract: Attempts have been made to use glycogen synthase kinase-3 beta (GSK3β) inhibitors for prophylactic treatment of neurocognitive conditions. However the use of lithium, a non-specific inhibitor of GSK3β results in mild cognitive impairment in humans. The effects of global GSK3β inhibition or knockout on learning and memory in healthy adult mice are also inconclusive. Our study aims to better understand the role of GSK3β in learning and memory through a more regionally, targeted approach, specifically performing lentiviral-mediated knockdown of GSK3β within the dentate gyrus (DG). DG-GSK3β-silenced mice showed impaired contextual fear memory retrieval. However, cue fear memory, spatial memory, locomotor activity and anxiety levels were similar to control. These GSK3β-silenced mice also showed increased induction and maintenance of DG long-term potentiation (DG-LTP) compared to control animals. Thus, this region-specific, targeted knockdown of GSK3β in the DG provides better understanding on the role of GSK3β in learning and memory.
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chew
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore.
authors.forename: Jae Ryun
authors.initials: JR
authors.lastname: Ryu
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore.
authors.forename: Teclise
authors.initials: T
authors.lastname: Ng
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore Singapore, Singapore.
authors.forename: Ananya
authors.initials: A
authors.lastname: Dasgupta
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore Singapore, Singapore.
authors.forename: Sin Hui
authors.initials: SH
authors.lastname: Neo
authors.affiliation: Regenerative Medicine DPU, GlaxoSmithKline (China) R&D Co., Ltd. Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Regenerative Medicine DPU, GlaxoSmithKline (China) R&D Co., Ltd. Shanghai, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore ; Behavioural Neuroscience Laboratory, National Neuroscience Institute Singapore, Singapore.
authors.forename: Zoë
authors.initials: Z
authors.lastname: Bichler
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore Singapore, Singapore.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sajikumar
authors.affiliation: Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore ; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore Singapore, Singapore ; KK Research Center, KK Women's and Children's Hospital Singapore, Singapore.
authors.forename: Eyleen L K
authors.initials: EL
authors.lastname: Goh
keywords: GSK-3β; LTP; contextual or spatial memory; dentate gyrus; lentivirus