Lin28a is Essential for Synaptic Plasticity in Dentate Granule Cells and Spatial Memory
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LETTER TO THE EDITOR
Lin28a is Essential for Synaptic Plasticity in Dentate Granule Cells and Spatial Memory Zhechun Hu1 • Jiao Ma2 • Yan Gu1,3
Received: 26 April 2020 / Accepted: 24 July 2020 Ó Shanghai Institutes for Biological Sciences, CAS 2020
Dear Editor, The dentate gyrus (DG), a subregion of the hippocampus, is involved in multiple physiological functions such as cognition and mood regulation. Dentate granule cells (DGCs), the primary neurons in the DG, are essential for coding spatial and contextual memories in the hippocampal neural circuits. The entorhinal cortex provides a majority of cortical projections to the DG via the perforant path, and forms synaptic connections with DGCs within the outer two-thirds of the molecular layer of the DG [1]. The plasticity of the perforant path-to-DGC synapses strengthens the connections of ensembles encoding spatial, contextual, or temporal information, and promotes the recall of related memories when certain perforant path inputs are reactivated [2]. Thus, the cellular metabolism underlying the synaptic plasticity in DGCs is important for regulating the physiological functions of these neurons in hippocampus-dependent behaviors. Lin28, a conserved RNA binding protein, has been reported to regulate a variety of biological processes, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12264-020-00591-7) contains supplementary material, which is available to authorized users. & Yan Gu [email protected] 1
Center of Stem Cell and Regenerative Medicine, Department of Neurology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
2
Interdisciplinary Institute of Neuroscience and Technology, Zhejiang University School of Medicine, Hangzhou 310029, China
3
Zhejiang Provincial Key Laboratory of Tissue Engineering and Regenerative Medicine, Hangzhou 310058, China
including tissue lineage and growth, metabolism, somatic cell reprogramming, and cancers [3]. Lin28a and Lin28b, the two homologs of Lin28, are expressed in the mammalian central nervous system during early development, but decline sharply after birth [4]. It has been recently reported that Lin28a remains in the neural stem cells in the adult brain, regulating their proliferation [5, 6]. However, it remains unclear whether and how Lin28 may regulate the synaptic plasticity and physiological functions of mature neurons. To address this question, we specifically knocked out Lin28a from mature DGCs by infusing an adeno-associated virus (AAV) expressing Cre recombinase driven by the CamKII promoter (AAV-CamKII-Cre-GFP) into the DG of adult Lin28aflox/flox mice (Lin28a-/-), while AAV-CamKIIGFP was used as control (Ctrl) (Fig. 1A, B). Two weeks after AAV injection, we dissected the hippocampus from these mice, performed western blotting, and found that the expression of Lin28a was significantly reduced in the DG (Fig. 1C, D), suggesting successful deletion of Lin28a from a majority of the D
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