On the effect of social cue valence in contextual memory persistence.

Social cues are valuable sensorial stimuli to the acquisition and retrieval of contextual memories. Here, we asked whether the valence of social cues would impact the formation of contextual memories. Adult male C57/BL6 mice were exposed to either conditioned place preference (CPP) or avoidance (CPA). As positive stimuli we used social interaction with a female (IF), while interaction with a male CD1 mice (IM) was used as negative stimulus. Contextual memory was tested 24 h and 7 days after conditioning. Aggressive behavior of CD1, as well as interaction with the female were quantified along the conditioning sessions. IM, but not IF, was salient enough to induce contextual memory estimated by the difference between the time in the conditioned context during test and habituation. Next, we chose two odors with innate behavioral responses and opposite valence to narrow down the sociability to one of its sensorial sources of information - the olfaction. We used urine from females in proestrus (U) and 2,4,5-trimethyl thiazoline (TMT), a predator odor. TMT decreased and U increased the time in the conditioned context during the test performed 24 h and 7 days after conditioning. Taken together, our results suggest that contextual memories conditioned to social encounters are difficult to stablish in mice, specially the one with positive valence. On the other hand, using odors with ecological relevance is a promising strategy to study long-term contextual memories with opposite valences. Ultimately, the behavioral protocol proposed here offers the advantage of studying contextual memories with opposite valences using unconditioned stimulus from the same sensorial category such as olfaction.

c-Fos expression predicts long-term social memory retrieval in mice.

The way the rodent brain generally processes socially relevant information is rather well understood. How social information is stored into long-term social memory, however, is still under debate. Here, brain c-Fos expression was measured after adult mice were exposed to familiar or novel juveniles and expression was compared in several memory and socially relevant brain areas. Machine Learning algorithm Random Forest was then used to predict the social interaction category of adult mice based on c-Fos expression in these areas. Interaction with a familiar co-specific altered brain activation in the olfactory bulb, amygdala, hippocampus, lateral septum and medial prefrontal cortex. Remarkably, Random Forest was able to predict interaction with a familiar juvenile with 100% accuracy. Activity in the olfactory bulb, amygdala, hippocampus and the medial prefrontal cortex were crucial to this prediction. From our results, we suggest long-term social memory depends on initial social olfactory processing in the medial amygdala and its output connections synergistically with non-social contextual integration by the hippocampus and medial prefrontal cortex top-down modulation of primary olfactory structures.

Mapping fear memory consolidation and extinction-specific expression of JunB.

Understanding the molecular and cellular process specifically regulated during fear memory consolidation and extinction is a critical step toward development of new strategies in the treatment of human fear disorders. Here we used inhibitory component of AP-1 transcription factor, JunB, in order to map brain regions where JunB-dependent transcription is regulated during consolidation and extinction of contextual fear memory. We found that contextual fear memory consolidation induced JunB expression in the medial nucleus and intercalated cells of the amygdala while extinction training induced JunB in the CA1 and CA3 areas of the dorsal hippocampus. JunB upregulation induced by contextual fear memory extinction was absent in alphaCaMKII autophosphorylation-deficient mice which have impaired contextual fear memory extinction. Thus, our data suggest that JunB expression in the medial nucleus and intercalated cells of the amygdala is involved in fear memory consolidation while alphaCaMKII-autophosphorylation-dependent JunB expression in the areas CA1 and CA3 of the dorsal hippocampus regulates fear memory extinction.