Role of the neural cell adhesion molecule (NCAM) in amygdalo-hippocampal interactions and salience determination of contextual fear memory

Abstract

Evidence suggests that the neural cell adhesion molecule (NCAM) is an important molecular constituent of adaptive and maladaptive circuit (re-)organization in the central nervous system. Here, we further investigate its putative involvement in amygdala and hippocampus functions during context fear memory formation. Using laser capture microdissection and quantitative RT-PCR, we show high NCAM mRNA expression levels in the lateral and basolateral subnuclei of the amygdala, as well as their training intensity- and context-dependent regulation during fear memory consolidation. Moreover, we demonstrate that deficits of NCAM-/- mice in context fear memory can be overcome through contextual pre-exposure, i.e. by reducing the modulatory influence of the amygdala on this hippocampus-dependent memory. On the contrary, NCAM-/- mice failed to increase contextual fear memory after salient overtraining, although they adequately increased their response to auditory-cued fear stimuli. Finally, we demonstrate a reduction of amygdalo-hippocampal theta synchronization in NCAM-/- mice during fear memory retrieval. Together, these results suggest an involvement of NCAM-mediated cell recognition processes in information processing of the amygdalo-hippocampal system and in the amygdala-mediated modulation of context fear memory according to stimulus salience.