title: Transgenic mice lacking NMDAR-dependent LTD exhibit deficits in behavioral flexibility.
abstract: While most studies have focused on the role of long-term potentiation in behavior, far less is known about the role of long-term depression (LTD). To examine the potential involvement of LTD in learning and memory, we generated transgenic mice that express a fragment of the SV40 small t antigen known to inhibit protein phosphatase 2A (PP2A). Small t antigen expression blocked both stimulus-induced and chemically induced NMDAR-dependent LTD at Schaffer collateral synapses but did not affect potentiation, depotentiation, or mGluR-dependent LTD. This physiological phenotype was associated with deficits in behavioral flexibility in both the Morris water maze and a delayed nonmatch to place T-maze task, suggesting that NMDAR-dependent LTD is required for behavioral flexibility and may act by weakening previously encoded memory traces when new information is learned.
authors.affiliation: Center for Neurobiology & Behavior, Columbia University, New York, NY 10032, USA.
authors.forename: Russell E
authors.initials: RE
authors.lastname: Nicholls
authors.forename: Juan Marcos
authors.initials: JM
authors.lastname: Alarcon
authors.forename: Gaël
authors.initials: G
authors.lastname: Malleret
authors.forename: Reed C
authors.initials: RC
authors.lastname: Carroll
authors.forename: Michael
authors.initials: M
authors.lastname: Grody
authors.forename: Svetlana
authors.initials: S
authors.lastname: Vronskaya
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate