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Cold Spring Harbor Laboratory Press, Learning & Memory, 1(20), p. 11-20, 2012

DOI: 10.1101/lm.027383.112

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The E3 ligase APC/C–Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice

Journal article published in 2012 by Joseph E. Pick, Marcos Malumbres ORCID, Eric Klann
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

The anaphase promoting complex/cyclosome (APC/C) is an E3 ligase regulated by Cdh1. Beyond its role in controlling cell cycle progression, APC/C–Cdh1 has been detected in neurons and plays a role in long-lasting synaptic plasticity and long-term memory. Herein, we further examined the role of Cdh1 in synaptic plasticity and memory by generating knockout mice where Cdh1 was conditionally eliminated from the forebrain post-developmentally. Although spatial learning and memory in the Morris water maze (MWM) was normal, the Cdh1 conditional knockout (cKO) mice displayed enhanced reversal learning in the MWM and in a water-based Y maze. In addition, we found that the Cdh1 cKO mice had impaired associative fear memory and exhibited impaired long-term potentiation (LTP) in amygdala slices. Finally, we observed increased expression of Shank1 and NR2A expression in amygdalar slices from the Cdh1 cKO mice following the induction of LTP, suggesting a possible molecular mechanism underlying the behavioral and synaptic plasticity impairments displayed in these mice. Our findings are consistent with a role for the APC/C–Cdh1 in fear memory and synaptic plasticity in the amygdala.