BACKGROUND: Changes in synaptic efficacy are believed to mediate the processes of learning and memory formation. Accumulating evidence implicates cell adhesion molecules in activity-dependent synaptic modifications associated with long-term potentiation (LTP); however, there is no precedence for the selective role of this molecule class in long-term depression (LTD). The mechanisms that modulate these processes still remain unclear. RESULTS: We report a novel role for glycosylphosphatidyl inositol (GPI)-anchored contactin in hippocampal CA1 synaptic plasticity. Contactin selectively supports paired-pulse facilitation (PPF) and NMDA (N-methyl-D-aspartate) receptor-dependent LTD but is not required for synaptic morphology, basal transmission, or LTP. Molecular analyses indicate that contactin is essential for the membrane and synaptic targeting of the contactin-associated protein (Caspr/paranodin) and for the proper distribution of a presumptive ligand, receptor protein tyrosine phosphatase beta (RPTPbeta)/phosphacan. CONCLUSIONS: These results indicate that contactin plays a selective role in synaptic plasticity and identify PPF and LTD, but not LTP, as contactin-dependent processes. Engagement of the contactin-Caspr complex with RPTPbeta may thus regulate cell-cell interactions contributing to specific synaptic plasticity forms.
BACKGROUND: Changes in synaptic efficacy are believed to mediate the processes of learning and memory formation. Accumulating evidence implicates cell adhesion molecules in activity-dependent synaptic modifications associated with long-term potentiation (LTP); however, there is no precedence for the selective role of this molecule class in long-term depression (LTD). The mechanisms that modulate these processes still remain unclear. RESULTS: We report a novel role for glycosylphosphatidyl inositol (GPI)-anchored contactin in hippocampal CA1 synaptic plasticity. Contactin selectively supports paired-pulse facilitation (PPF) and NMDA (N-methyl-D-aspartate) receptor-dependent LTD but is not required for synaptic morphology, basal transmission, or LTP. Molecular analyses indicate that contactin is essential for the membrane and synaptic targeting of the contactin-associated protein (Caspr/paranodin) and for the proper distribution of a presumptive ligand, receptor protein tyrosine phosphatase beta (RPTPbeta)/phosphacan. CONCLUSIONS: These results indicate that contactin plays a selective role in synaptic plasticity and identify PPF and LTD, but not LTP, as contactin-dependent processes. Engagement of the contactin-Caspr complex with RPTPbeta may thus regulate cell-cell interactions contributing to specific synaptic plasticity forms.
Authors: Sandra D Santos; Olga Iuliano; Luís Ribeiro; Julien Veran; Joana S Ferreira; Pedro Rio; Christophe Mulle; Carlos B Duarte; Ana Luísa Carvalho Journal: J Biol Chem Date: 2012-01-05 Impact factor: 5.157
Authors: Thomas Fernandez; Thomas Morgan; Nicole Davis; Ami Klin; Ashley Morris; Anita Farhi; Richard P Lifton; Matthew W State Journal: Am J Hum Genet Date: 2004-04-21 Impact factor: 11.025
Authors: Alison G Compton; Douglas E Albrecht; Jane T Seto; Sandra T Cooper; Biljana Ilkovski; Kristi J Jones; Daniel Challis; David Mowat; Barbara Ranscht; Melanie Bahlo; Stanley C Froehner; Kathryn N North Journal: Am J Hum Genet Date: 2008-11-20 Impact factor: 11.025
Authors: Anilkumar M Pillai; German P Garcia-Fresco; Aurea D Sousa; Jeffrey L Dupree; Benjamin D Philpot; Manzoor A Bhat Journal: J Neurosci Res Date: 2007-08-15 Impact factor: 4.164