Time-course of systems consolidation and fear memory generalization in adolescent rats of different sex

Systems consolidation is a time-dependent process in which the retrieval of contextual memories becomes progressively independent from the hippocampus and more reliant on cortical structures. One qualitative consequence, supposed to be causally related, is the progressive loss of memory precision. Memory generalization, however, is a much more complex phenomena, and may take place much faster in adult animals, for instance, in response to changes in the available levels of sex hormones. In this sense, females are known to display a generalized memory earlier than males. Sex differences might have an important role in the modulation of mnemonic processes, and despite being of paramount importance for the understanding of the cognitive dynamics of juveniles, it remains poorly investigated. Here, we studied adolescent rats (P42-49) of different sex comparing the natural time-course of systems consolidation as verified both by the hippocampus-dependency and the onset of memory generalization. Contextual fear discrimination was quantified at different time-points after learning (2, 7, 14, 21 and 28 days). Our results demonstrated that, contrary to what is observed in adults, memory generalization occurs earlier in adolescent males (14 days) than in females (28 days). During adolescence, females display a higher mean discrimination index at all time-points, suggesting that they retain a more detailed memory. Likewise, pre-test pharmacological inactivation of the hippocampus (with GABAA agonist muscimol) was able to impair memory retrieval in females, but not in males, 14 days after training. These results support a causal relationship between memory generalization and retrieval independence from the hippocampus in male adolescent rats. However, both aspects of the systems consolidation process appear to be distinctly modulated in animals of different sex, with males (and ovariectomized females) enduring an accelerated onset of both memory precision loss and the hippocampus independence compared to females, suggesting a clear role for gonadal hormones in this cognitive corticalization process.