Impaired Sociability and Cognitive Function in Nrcam-null Mice

NRCAM (Neuronal Cell Adhesion Molecule) has an important role in axonal guidance and the organization of neural circuitry during brain development. Association analyses in human populations have identified NRCAM as a candidate gene for autism susceptibility. In the present study, we evaluated Nrcam-null mice for sociability, social novelty preference, and reversal learning as a model for the social deficits, repetitive behavior, and cognitive rigidity characteristic of autism. Prepulse inhibition of acoustic startle responses was also measured, to reflect sensorimotor-gating deficits in autism spectrum disorders. Assays for anxiety-like behavior in an elevated plus maze and open field, motor coordination, and olfactory ability in a buried food test were conducted to provide control measures for the interpretation of results. Overall, the loss of Nrcam led to behavioral alterations in sociability, acquisition of a spatial task, and reversal learning, dependent on sex. In comparison to male wild type mice, male Nrcam-null mutants had significantly decreased sociability in a three-chambered choice task. Low sociability in the male null mutants was not associated with changes in anxiety-like behavior, activity, or motor coordination. Male, but not female, Nrcam-null mice had small decreases in prepulse inhibition. Nrcam deficiency in female mice led to impaired acquisition of spatial learning in the Morris water maze task. Reversal learning deficits were observed in both male and female Nrcam-null mice. These results provide evidence that NRCAM mediates domains of function relevant to symptoms observed in autism.