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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Amygdala / cytology
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Amygdala / physiology*
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Analysis of Variance
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Calcium-Calmodulin-Dependent Protein Kinase Kinase / genetics
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Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism
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Cdh1 Proteins
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Cell Cycle Proteins / deficiency
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Cell Cycle Proteins / metabolism*
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Electric Stimulation
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Exploratory Behavior / physiology
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Fear / physiology*
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Gene Expression Regulation / genetics
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Hippocampus / cytology
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Hippocampus / physiology
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Inhibition, Psychological
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Long-Term Potentiation / genetics
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Long-Term Potentiation / physiology*
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Maze Learning / physiology
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Memory / physiology*
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Mice
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Mice, Knockout
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Motor Activity / genetics
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Nerve Tissue Proteins / metabolism
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Neurons / cytology
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Post-Synaptic Density / metabolism
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Receptors, N-Methyl-D-Aspartate / metabolism
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Synaptosomes / metabolism
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Ubiquitin-Protein Ligase Complexes / metabolism*
Substances
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Cdh1 Proteins
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Cell Cycle Proteins
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Fzr1 protein, mouse
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NR2A NMDA receptor
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Nerve Tissue Proteins
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Receptors, N-Methyl-D-Aspartate
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Shank2 protein, mouse
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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Calcium-Calmodulin-Dependent Protein Kinase Kinase