Multiple context discrimination in adult rats: sex variability and dynamics of time-dependent generalization of an aversive memory

Abstract

Memory generalization can be defined as the transference of a conditioned fear response to novel contexts. It can be attained rapidly, by manipulating distinct hormonal and neurotransmitter systems, but, more importantly, in a time-dependent manner the interval between training and test sessions affects the quality of retrieved memory, due to a rearrangement in the recruitment of brain regions, as is the case in Systems Consolidation. However, less is known about how female and male subjects retrieve contextual memories over time. In this work, we aimed to investigate how rats of both sexes discriminate among multiple contexts gradually differentiated in similarity to the conditioning one, two days after training. In the pilot study, despite not obtaining, at first, a stepwise series of freezing responses, we found that, strangely, males displayed their higher levels of freezing to the least similar context, while females systematically displayed lower freezing levels compared to males as if they were better discriminators when tested in exact same contexts. With a second set of contexts, sorted according to other criteria, only males, at the 2 days interval, attained a staircase-like response to the successive contexts, while females displayed a completely different freezing pattern; in remote tests, 28 and 45 days later, freezings grouped into two levels, suggesting a partial time-dependent generalization for some of the contexts. Females and males, in discriminating between multiple, dissimilar aversive contexts, seem to deal with threat signals in distinct ways, through different sensory modalities, a clear demonstration of behavioural dimorphism.