Regulation of hippocampal cell adhesion molecules NCAM and L1 by contextual fear conditioning is dependent upon time and stressor intensity

Cell adhesion molecules (CAMs) of the immunoglobulin superfamily, NCAM and L1, as well as the post-translational addition of alpha-2,8-linked polysial ic acid (PSA) homopolymers to NCAM (PSA-NCAM), have been implicated in the neural mechanisms underlying memory formation. Given that the degree of str ess elicited by the training situation is one of the key factors that influ ence consolidation processes, this study questioned whether training rats u nder different stressor intensities (0.2, 0.4, or 1 mA shock intensity) in a contextual fear conditioning task might regulate subsequent expression of NCAM, PSA-NCAM and L1 in the hippocampus, as evaluated immediately after t esting rats for conditioning at 12 and 24h after training. Behavioural inhi bition (evaluated as a 'freezing' index) at testing and post-testing plasma corticosterone levels were also assessed. The results showed that 12 h pos t-training, conditioned animals displayed reduced NCAM, but increased L1, e xpression. At this time point, the group trained at the highest shock inten sity (1 mA) also presented decreased PSA-NCAM expression. Analyses performe d 24h post-training indicated that the 1 mA group exhibited increased NCAM and L1 expression, but decreased expression of PSA-NCAM levels. In addition , L1 values that presented a shock intensity-dependent U-shaped pattern wer e also increased in the group trained at the lowest shock condition (0.2 mA ) and remained unchanged in the intermediate shock condition (0.4 mA). Free zing and corticosterone values at both testing times were positively relate d with shock intensity experienced at training. Therefore, our results show a complex regulation of CAMs of the immunoglobulin superfamily in the hipp ocampus that depends upon stressor intensity and time factors. In addition, the pattern of CAMs expression found in the 1 mA group (which is the one t hat shows higher post-training corticosterone levels and develops the stron ger and longer-lasting levels of fear conditioning) supports the view that, after a first phase of synaptic de-adherence during consolidation, NCAM an d L1 might participate in the stabilization of selected synapses underlying the establishment of long-term memory for contextual fear conditioning, an d suggests that glucocorticoids might play a role in the observed regulatio n of CAMs.