A synthetic peptide ligand of NCAM affects exploratory behavior and memory in rodents

The neural cell adhesion molecule (NCAM) is an important modulator of neuronal development and plasticity associated with learning and memory. Previously, a synthetic peptide ligand of NCAM, called C3, has been identified and shown to modulate neuronal plasticity in vitro and memory in a step-through passive avoidance task in rats in vivo. In this study, we extended these findings and found that intraventricular injection of C3 prior to training impaired learning or memory processes in rats and mice in an approach avoidance task and decreased exploratory behavior in rats. The effect of C3 was additionally evaluated in the Morris water maze; memory impairment was observed in the second training trial 24 h after the injection of C3 only, indicating an effect on short-term memory. The C3-mediated memory impairment observed in the approach avoidance and water maze tests is suggested to be the result of C3-inhibiting NCAM functions in the brain. This study demonstrates that it is possible to modulate learning/memory processes in rodents in vivo with small synthetic NCAM-binding peptides that induce developmental plasticity in vitro.