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N-cadherin regulates molecular organization of excitatory and inhibitory synaptic circuits in adult hippocampus in vivo.

Authors
  • Nikitczuk, Jessica S1
  • Patil, Shekhar B1
  • Matikainen-Ankney, Bridget A1
  • Scarpa, Joseph1
  • Shapiro, Matthew L1
  • Benson, Deanna L1
  • Huntley, George W1
  • 1 Fishberg Department of Neuroscience, Friedman Brain Institute and The Graduate School of Biomedical Sciences, The Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY 10029.
Type
Published Article
Journal
Hippocampus
Publisher
Wiley (John Wiley & Sons)
Publication Date
Aug 01, 2014
Volume
24
Issue
8
Pages
943–962
Identifiers
DOI: 10.1002/hipo.22282
PMID: 24753442
Source
Medline
Keywords
License
Unknown

Abstract

N-Cadherin and β-catenin form a transsynaptic adhesion complex required for spine and synapse development. In adulthood, N-cadherin mediates persistent synaptic plasticity, but whether the role of N-cadherin at mature synapses is similar to that at developing synapses is unclear. To address this, we conditionally ablated N-cadherin from excitatory forebrain synapses in mice starting in late postnatal life and examined hippocampal structure and function in adulthood. In the absence of N-cadherin, β-catenin levels were reduced, but numbers of excitatory synapses were unchanged, and there was no impact on number or shape of dendrites or spines. However, the composition of synaptic molecules was altered. Levels of GluA1 and its scaffolding protein PSD95 were diminished and the density of immunolabeled puncta was decreased, without effects on other glutamate receptors and their scaffolding proteins. Additionally, loss of N-cadherin at excitatory synapses triggered increases in the density of markers for inhibitory synapses and decreased severity of hippocampal seizures. Finally, adult mutant mice were profoundly impaired in hippocampal-dependent memory for spatial episodes. These results demonstrate a novel function for the N-cadherin/β-catenin complex in regulating ionotropic receptor composition of excitatory synapses, an appropriate balance of excitatory and inhibitory synaptic proteins and the maintenance of neural circuitry necessary to generate flexible yet persistent cognitive and synaptic function.

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