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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.

Pubmed ID: 19540269

Authors

  • Moy SS
  • Nonneman RJ
  • Young NB
  • Demyanenko GP
  • Maness PF

Journal

Behavioural brain research

Publication Data

December 14, 2009

Associated Grants

  • Agency: NICHD NIH HHS, Id: P30 HD003110
  • Agency: NICHD NIH HHS, Id: P30 HD003110-41
  • Agency: NICHD NIH HHS, Id: P30 HD03110
  • Agency: NIMH NIH HHS, Id: U54 MH066418
  • Agency: NIMH NIH HHS, Id: U54 MH066418-05
  • Agency: NIMH NIH HHS, Id: U54 MH66418

Mesh Terms

  • Animals
  • Anxiety
  • Autistic Disorder
  • Cell Adhesion Molecules
  • Cohort Studies
  • Disease Models, Animal
  • Female
  • Learning Disorders
  • Male
  • Maze Learning
  • Mental Disorders
  • Mice
  • Mice, Knockout
  • Neuropsychological Tests
  • Reversal Learning
  • Sex Characteristics
  • Social Behavior
  • Social Behavior Disorders
  • Space Perception