Tônus inibitório da região CA2 do hipocampo na memória social de camundongos machos e fêmeas

Abstract

Sensory characteristics that identify an individual are stored in social memory (SM), whose processing depends on the CA2 region of the hippocampus. Unlike other regions of the hippocampus, the CA2 region remains tonically inhibited by mechanisms involving the activation of cannabinoid receptors. Considering the unique characteristics of the CA2 region and the different social demands for males and females, we investigated the effect of the CB1 receptor antagonist on the SM of C57/Bl6 male and female mice. The animals underwent the social recognition test, consisting of two successive encounters (training, TR; test, TT), separated by 24 hours, with a juvenile of the same sex. Females and males recognized the juvenile as familiar because they interacted with the juvenile for less time in the test session. However, pre-TT and intra-CA2 administration of AM251, a CB1 antagonist, impaired the recall of SM in both sexes. Next, we wondered if the condition of social isolation (SI), known to impair SM, could alter the inhibitory tone of CA2. Males and females were kept in groups of 5 animals per cage (GC) or isolated for 7 days (SI). After confirming that SI impairs SM in C57/BL6 animals, we performed immunofluorescence to estimate inhibitory tone by labeling GABAergic neurons. We delimited CA2 by marking purkinje cell protein 4 (PCP4) and identified a lower number of positive neurons for glutamate decarboxylase 67 (GAD67), only in isolated males. This result suggests that SI may be reducing the inhibitory tone in the CA2 region. Together, our results support the conclusion that disinhibition of the CA2 region of the hippocampus compromises the processing of information related to conspecifics, possibly through mechanisms that differ between males and females.