title: N-glycosylation in the hippocampus is required for the consolidation and reconsolidation of contextual fear memory.
abstract: Memory consolidation and reconsolidation have been shown to require new gene expression. N-glycosylation, one of the major post-translational modifications, is known to play essential or regulatory roles in protein function. A previous study suggested that N-glycosylation is required for the maintenance of long-term potentiation in hippocampal CA1 neurons. However, the role of de novo N-glycosylation in learning and memory, such as memory consolidation and reconsolidation, still remains unclear. Here, we show critical roles for N-glycosylation in the consolidation and reconsolidation of contextual fear memory in mice. We examined the effects of pharmacological inhibition of N-glycosylation in the hippocampus on these memory processes using three different inhibitors (tunicamycin, 1-deoxynojirimycin, and swainsonine) that block the enzymatic activity required for N-glycosylation at different steps. Microinfusions of the N-glycosylation inhibitors into the dorsal hippocampus impaired long-term memory (LTM) formation without affecting short-term memory (STM). Similarly, this pharmacological blockade of N-glycosylation in the dorsal hippocampus also disrupted post-reactivation LTM after retrieval without affecting post-reactivation STM. Additionally, a microinfusion of swainsonine blocked c-fos induction in the hippocampus, which is observed when memory is consolidated. Our observations showed that N-glycosylation is required for the consolidation and reconsolidation of contextual fear memory and suggested that N-glycosylation contributes to the new gene expression necessary for these memory processes.
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Inaba
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kai
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Tokyo, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan. Electronic address: kida@nodai.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D005964:Glucosyltransferases / Q000378:metabolism; D006031:Glycosylation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D005964:Glucosyltransferases
keywords: 1-Deoxynojirimycin; Fear conditioning; N-glycosylation; Swainsonine; Tunicamycin; c-fos