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Transgenic Mice Lacking NMDAR-Dependent LTD Exhibit Deficits in Behavioral Flexibility
Journal Title
Neuron
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2008-04
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58
Publication Issue
1
Publication Begin
104
Publication End
117
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PIIS0896627308001724.pdf
Adobe PDF, 1.48 MB
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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.
Citation
Nicholls RE, Alarcon JM, Malleret G, Carroll RC, Grody M, Vronskaya S, Kandel ER. Transgenic mice lacking NMDAR-dependent LTD exhibit deficits in behavioral flexibility. Neuron. 2008 Apr 10;58(1):104-17. doi: 10.1016/j.neuron.2008.01.039. PMID: 18400167.