CONICET | Buscador de Institutos y Recursos Humanos

It is now very well stated that consolidation is the process by which new information is encoded in neural circuits. However, once a memory is consolidated it does not remain stable indefinitely. Not only can it change with time but also with experience. In particular, when a reminder of the learning event is presented to an animal that has learnt something new, the memory and thus the neural circuits that encode that memory become labile and need a process of reconsolidation to be re-stabilized. This is crucial for the modification of existing memories as it enables changes in its strength and/or content. For the past decades, labilization/reconsolidation processes have been extensively studied from behavioral, cellular and molecular approaches but no whole-brain studies have emerged to elucidate neural circuits and brain areas subserving memory dynamics during these processes in small animals. In this work, we studied the male mouse brain from a functional perspective using small-animal Positron Emission Tomography (PET), and [18F]-deoxyglucose (FDG) as the radioactive compound, thus measuring differential glucose consumption. The main objective was to study which brain areas were involved in labilization/reconsolidation of fear memory using a contextual fear conditioning paradigm in mice. For that purpose we injected the mice with FDG intraperitoneally at different times pre/post re-exposure to the training context, then anesthetized the mice with isoflurane and acquired images through a PET scanner. We found differences in glucose consumption mainly in zones comprising the ectorhinal cortex, the temporal association cortex, hippocampus and amygdala in re-exposed animals compared to non-re-exposed animals. The differences in glucose consumption showed a marked temporal course, were context-specific, and were either hyper- or hypo-consumptions. Moreover, animals that only evoked but did not labilized the memory trace showed significant differences compared to mice that labilized and reconsolidated. Our work opens new insights in the study of the dynamics of activation of brain areas during memory labilization/reconsolidation by using a novel technique for the field, which in combination with others like immunofluorescence, DREADDS and electrophysiology helps to unravel the pending question about circuits involved in labilization/reconsolidation.