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

Learn Mem. 2012 Dec 14;20(1):11-20. doi: 10.1101/lm.027383.112.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / cytology
  • Amygdala / physiology*
  • Analysis of Variance
  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism
  • Cdh1 Proteins
  • Cell Cycle Proteins / deficiency
  • Cell Cycle Proteins / metabolism*
  • Electric Stimulation
  • Exploratory Behavior / physiology
  • Fear / physiology*
  • Gene Expression Regulation / genetics
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Inhibition, Psychological
  • Long-Term Potentiation / genetics
  • Long-Term Potentiation / physiology*
  • Maze Learning / physiology
  • Memory / physiology*
  • Mice
  • Mice, Knockout
  • Motor Activity / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • Post-Synaptic Density / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Synaptosomes / metabolism
  • Ubiquitin-Protein Ligase Complexes / metabolism*


  • Cdh1 Proteins
  • Cell Cycle Proteins
  • Fzr1 protein, mouse
  • NR2A NMDA receptor
  • Nerve Tissue Proteins
  • Receptors, N-Methyl-D-Aspartate
  • Shank2 protein, mouse
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase