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Neuron. 2008 Apr 10;58(1):104-17. doi: 10.1016/j.neuron.2008.01.039.

Transgenic mice lacking NMDAR-dependent LTD exhibit deficits in behavioral flexibility.

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Center for Neurobiology & Behavior, Columbia University, New York, NY 10032, USA.


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.

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