Role of stress system disturbance and enhanced novelty response in spatial learning of NCAM-deficient mice.

The neural cell adhesion molecule (NCAM) plays a crucial role in stress-related brain function, emotional behavior and memory formation. In this study, we investigated the functions of the glucocorticoid and serotonergic systems in mice constitutively deficient for NCAM (NCAM-/- mice). Our data provide evidence for a hyperfunction of the hypothalamic-pituitary-adrenal axis, with enlarged adrenal glands and increased stress-induced corticosterone release, but reduced hippocampal glucocorticoid receptor expression in NCAM-/- mice when compared to NCAM+/+ mice. We also obtained evidence for a hypofunction of 5-HT1A autoreceptors as indicated by increased 8-0H-DPAT-induced hypothermia. These findings suggest a disturbance of both humoral and neural stress systems in NCAM-/- mice. Accordingly, we not only confirmed previously observed hyperarousal of NCAM-/- mice in various anxiety tests, but also observed an increased response to novelty exposure in these animals. Spatial learning deficits of the NCAM-/- mice in a Morris Water maze persisted, even when mice were pretrained to prevent effects of novelty or stress. We suggest that NCAM-mediated processes are involved in both novelty/stress-related emotional behavior and in cognitive function during spatial learning.

Novelty-induced behavioral traits correlate with numbers of brainstem noradrenergic neurons and septal cholinergic neurons in C57BL/6J mice.

It is generally accepted that different brain regions regulate specific behavioral responses and that structural alterations in these regions may affect behavior. We investigated whether inter-individual variability in novelty-induced behaviors in C57BL/6J mice correlates with numbers of noradrenergic neurons in the locus coeruleus and cholinergic neurons in the septum. We found that exploration of new stimuli correlated negatively with numbers of noradrenergic neurons, whereas anxiety correlated positively with numbers of cholinergic neurons. The observed correlations suggest physiologically plausible links between structure and function and indicate that precise morphological estimates can be predictive for behavioral responses.

Ethological analysis of the senescence-accelerated P/8 mouse.

Behaviour of senescence-accelerated (P/8) and resistant (R/1) mice was assessed using an ethological approach in a longitudinal study for exploratory and anxiety related behaviours (home cage activity, open field, elevated plus-maze and new object tests), cognitive abilities (step-down and step-through passive avoidance and water maze tests) and visual acuity (visible cliff test). Overall, P/8 mice showed higher activity induced by new environmental stimuli, higher anxiety and lower novelty seeking behaviour in the new object test than R/1 mice. P/8 mice showed an impaired performance as compared to R/1 mice in two passive avoidance tasks. Behavioural alterations of P/8 mice were already apparent at the age of 10-12 weeks. Factor analyses indicated that the impairment of P/8 mice in passive avoidance tasks relates to their altered exploratory and anxiety-related behaviour rather than to cognitive impairments. In the water maze, both strains performed badly in the visible platform task, suggesting poor visual abilities in both strains as supported by the visible cliff test. We conclude that, for a better interpretation of cognitive abilities of P/8 mice, tests not based on novelty-induced behaviour, visual acuity and good motor skills should be used. Finally, we question whether P/8 mice could be a model of some forms of neuropsychiatric disorders resulting from developmental abnormalities rather than aging.