title: Impairment of hippocampal long-term potentiation and failure of learning in mice treated with d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol.
abstract: Gangliosides (sialic acid-containing glycosphingolipids) play important roles in many physiological functions, including synaptic plasticity in the hippocampus, which has been suggested as the basal cellular process of learning and memory in the brain. In the present study, long-term potentiation (LTP) and long-term depression (LTD) in CA1 hippocampal neurons and learning behavior were examined in mice treated with (D)-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol ((D)-PDMP), an inhibitor of ganglioside biosynthesis. Mice treated with (D)-PDMP, but not those treated with (L)-PDMP, showed impairment of LTP induction in hippocampal CA1 neurons without any significant change in LTD formation and also showed a failure of learning in the 4-pellet taking test. These results indicate that de novo synthesis of gangliosides in the brain is involved in synaptic plasticity of LTP in mouse hippocampal CA1 neurons and plays important roles in learning and memory.
authors.affiliation: Department of Physiology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Kotaro
authors.initials: K
authors.lastname: Ikarashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Goto
authors.forename: Kenya
authors.initials: K
authors.lastname: Kaneko
authors.forename: Makoto
authors.initials: M
authors.lastname: Sugita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Jin-Ichi
authors.initials: J
authors.lastname: Inokuchi
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005732:Gangliosides / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D005732:Gangliosides; D009025:Morpholines; C033110:RV 538