title: Facilitation of NMDAR-independent LTP and spatial learning in mutant mice lacking ryanodine receptor type 3.
abstract: To evaluate the role in synaptic plasticity of ryanodine receptor type 3 (RyR3), which is normally enriched in hippocampal area CA1, we generated RyR3-deficient mice. Mutant mice exhibited facilitated CA1 long-term potentiation (LTP) induced by short tetanus (100 Hz, 100 ms) stimulation. Unlike LTP in wild-type mice, this LTP was not blocked bythe NMDA receptor antagonist D-AP5 but was partially dependent on L-type voltage-dependent Ca2+ channels (VDCCs) and metabotropic glutamate receptors (mGluRs). Long-term depression (LTD) was not induced in RyR3-deficient mice. RyR3-deficient mice also exhibited improved spatial learning on a Morris water maze task. These results suggest that in wild-type mice, in contrast to the excitatory role of Ca2+ influx, RyR3-mediated intracellular Ca2+ ([Ca2+]i) release from endoplasmic reticulum (ER) may inhibit hippocampal LTP and spatial learning.
authors.affiliation: Shionogi Institute for Medical Science, Shionogi and Company, Ltd., Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Futatsugi
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: H
authors.initials: H
authors.lastname: Ogura
authors.forename: S T
authors.initials: ST
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: Nagata
authors.forename: G
authors.initials: G
authors.lastname: Kuwajima
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Itohara
authors.forename: K
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D019837:Ryanodine Receptor Calcium Release Channel / Q000172:deficiency* / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D016194:Receptors, N-Methyl-D-Aspartate; D019837:Ryanodine Receptor Calcium Release Channel