Recovery of emotional behaviour in neural cell adhesion molecule (NCAM) null mutant mice through transgenic expression of NCAM180

In the present study we further investigate functions of the neural cell ad hesion molecule (NCAM) in the mature central nervous system and its implica tions for animal behaviour. To this end we generated transgenic mice expres sing the major NCAM isoform with the largest cytoplasmic domain, NCAM180, u nder control of a promoter for the small form neurofilament gene. Transgeni c mice were also bred with mice deficient in endogenous NCAM (Ncam(-/-) mic e) so that effects of NCAM180 could be analysed in the presence and absence of endogenous NCAM. While overexpression of transgenic NCAM180 was without apparent behavioural or morphological effect, its expression in Ncam(-/-) mice counteracted NCAM ablation-induced aggressive, anxiety-like and antide pressant-like behaviour. It furthermore prevented a hypersensitivity of Nca m(-/-) mice to the anxiolytic serotonin(1a) (5-HT1A) receptor agonist buspi rone. Such recovery of emotional behaviour and behavioural 5-HT1A response occurred in spite of misdevelopment of the olfactory bulb and hippocampus t hat is characteristic of Ncam(-/-) mice, and without an apparent change in the expression of 5-HT1A binding sites in the brain. Hippocampus- and amygd ala-dependent learning, though disturbed in Ncam(-/-) mice, remained unaffe cted by the transgenic NCAM180. We suggest an involvement of NCAM180-mediat ed cell recognition processes in the serotonergic modulation of emotional b ehaviour in adult mice.