A ROLE FOR THE CADHERIN FAMILY OF CELL-ADHESION MOLECULES IN HIPPOCAMPAL LONG-TERM POTENTIATION

The cadherins are a family of cell-cell adhesion molecules that mediat e Ca2+-dependent homophilic interactions between cells and transduce s ignals by interacting with cytoplasmic proteins. In the hippocampus, i mmunostaining combined with confocal microscopy revealed that both neu ral- (N-) and epithelial- (E-) cadherin are present at synaptic sites, implying a role in synaptic function. Pretreatment of hippocampal sli ces with antibodies (Abs) raised against the extracellular domain of e ither N-cad or E-cad had no effect on basal synaptic properties but si gnificantly reduced long-term potentiation (LTP). Infusion of antagoni stic peptides containing the His-Ala-Val (HAV) consensus sequence for cadherin dimerization also attenuated LTP induction without affecting previously established LTP. Because the intense synaptic stimulation a ssociated with LTP induction might transiently deplete extracellular C a2+ and hence potentially destabilize cadherin-cadherin interactions, we examined whether slices could be protected from inhibition by N-cad Abs or HAV peptides by raising the extracellular Ca2+ concentration. Indeed, we found that high extracellular Ca2+ prevented the block of L TP by these agents. Taken together, these results indicate that cadher ins are involved in synaptic plasticity, and the stability of cadherin -cadherin bonds may be regulated by synaptic stimulation.