Transgenic mice lacking NMDAR-dependent LTD exhibit deficits in behavioral flexibility.
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.
Nicholls
Russell E
RE
Center for Neurobiology & Behavior, Columbia University, New York, NY 10032, USA.
Alarcon
Juan Marcos
JM
Malleret
Gaël
G
Carroll
Reed C
RC
Grody
Michael
M
Vronskaya
Svetlana
S
Kandel
Eric R
ER
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
D016194:Receptors, N-Methyl-D-Aspartate