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Chew B, Ryu JR, Ng T, et al. Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity. Front Behav Neurosci. 2015;9:158doi: 10.3389/fnbeh.2015.00158.
Chew, B., Ryu, J. R., Ng, T., Ma, D., Dasgupta, A., Neo, S. H., Zhao, J., Zhong, Z., Bichler, Z., Sajikumar, S., & Goh, E. L. (2015). Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity. Frontiers in behavioral neuroscience, 9158. https://doi.org/10.3389/fnbeh.2015.00158
Chew, Benjamin, et al. "Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity." Frontiers in behavioral neuroscience vol. 9 (2015): 158. doi: https://doi.org/10.3389/fnbeh.2015.00158
Chew B, Ryu JR, Ng T, Ma D, Dasgupta A, Neo SH, Zhao J, Zhong Z, Bichler Z, Sajikumar S, Goh EL. Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity. Front Behav Neurosci. 2015 Jun 23;9:158. doi: 10.3389/fnbeh.2015.00158. eCollection 2015. PMID: 26157370; PMCID: PMC4477161.
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Front Behav Neurosci. 2015 Jun 23;9:158. doi: 10.3389/fnbeh.2015.00158. eCollection 2015.

Lentiviral silencing of GSK-3β in adult dentate gyrus impairs contextual fear memory and synaptic plasticity.

Frontiers in behavioral neuroscience

Benjamin Chew, Jae Ryun Ryu, Teclise Ng, Dongliang Ma, Ananya Dasgupta, Sin Hui Neo, Jing Zhao, Zhong Zhong, Zoë Bichler, Sreedharan Sajikumar, Eyleen L K Goh

Affiliations

  1. Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore.
  2. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore Singapore, Singapore.
  3. Regenerative Medicine DPU, GlaxoSmithKline (China) R&D Co., Ltd. Shanghai, China.
  4. Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School Singapore, Singapore ; Behavioural Neuroscience Laboratory, National Neuroscience Institute Singapore, Singapore.
  5. 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.

PMID: 26157370 PMCID: PMC4477161 DOI: 10.3389/fnbeh.2015.00158

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.

Keywords: GSK-3β; LTP; contextual or spatial memory; dentate gyrus; lentivirus

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