title: The E3 ligase APC/C-Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice.
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.
authors.affiliation: Center for Neural Science, New York University, New York, New York 10003, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Pick
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
authors.forename: Eric
authors.initials: E
authors.lastname: Klann
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000704:Analysis of Variance; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics / Q000378:metabolism; D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins / Q000172:deficiency / Q000378:metabolism*; D004558:Electric Stimulation; D005106:Exploratory Behavior / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007266:Inhibition, Psychological; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D057907:Post-Synaptic Density / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
chemical_list: D064200:Cdh1 Proteins; D018797:Cell Cycle Proteins; C577585:Fzr1 protein, mouse; C120997:NR2A NMDA receptor; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C488222:Shank2 protein, mouse; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase