Contactin supports synaptic plasticity associated with hippocampal long-term depression but not potentiation.
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.
Murai
Keith K
KK
The Burnham Institute, Neurobiology Program, La Jolla, CA 92037, USA.
Misner
Dinah
D
Ranscht
Barbara
B
D000818:Animals; D015153:Blotting, Western; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D058966:Contactins; D003712:Dendrites / Q000378:metabolism; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation; D008565:Membrane Proteins; D051379:Mice; D009154:Mutation; D009473:Neuronal Plasticity; D017966:Pyramidal Cells / Q000166:cytology / Q000648:ultrastructure; D011956:Receptors, Cell Surface / Q000378:metabolism; D018077:Receptors, Leukotriene / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*
D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D058966:Contactins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D018077:Receptors, Leukotriene; D016194:Receptors, N-Methyl-D-Aspartate; C412375:cysteinyl leukotriene receptor 2; C083169:leukotriene D4 receptor