Temporal Flexibility of Systems Consolidation and the Synaptic Occupancy/Reset Theory (SORT): Cues About the Nature of the Engram

The ability to adapt to new situations involves behavioral changes expressed either from an innate repertoire, or by acquiring experience through memory consolidation mechanisms, by far a much richer and flexible source of adaptation. Memory formation consists of two interrelated processes that take place at different spatial and temporal scales, Synaptic Consolidation, local plastic changes in the recruited neurons, and Systems Consolidation, a process of gradual reorganization of the explicit/declarative memory trace between hippocampus and the neocortex. In this review, we summarize some converging experimental results from our lab that support a normal temporal framework of memory systems consolidation as measured both from the anatomical and the psychological points of view, and propose a hypothetical model that explains these findings while predicting other phenomena. Then, the same experimental design was repeated interposing additional tasks between the training and the remote test to verify for any interference: we found that (a) when the animals were subject to a succession of new learnings, systems consolidation was accelerated, with the disengagement of the hippocampus taking place before the natural time point of this functional switch, but (b) when a few reactivation sessions reexposed the animal to the training context without the shock, systems consolidation was delayed, with the hippocampus prolonging its involvement in retrieval. We hypothesize that new learning recruits from a fixed number of plastic synapses in the CA1 area to store the engram index, while reconsolidation lead to a different outcome, in which additional synapses are made available. The first situation implies the need of a reset mechanism in order to free synapses needed for further learning, and explains the acceleration observed under intense learning activity, while the delay might be explained by a different process, able to generate extra free synapses: depending on the cognitive demands, it deals either with a fixed or a variable pool of available synapses. The Synaptic Occupancy/Reset Theory (SORT) emerged as an explanation for the temporal flexibility of systems consolidation, to encompass the two different dynamics of explicit memories, as well as to bridge both synaptic and systems consolidation in one single mechanism

Modelo do trion sobre processamento cortical da informação

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Soma de performances em treinos consecutivos na esquiva inibitória com choque de baixa intensidade

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Memory reconsolidation may be disrupted by a distractor stimulus presented during reactivation

Memories can be destabilized by the reexposure to the training context, and may reconsolidate into a modified engram. Reconsolidation relies on some particular molecular mechanisms involving LVGCCs and GluN2B-containing NMDARs. In this study we investigate the interference caused by the presence of a distractor - a brief, unanticipated stimulus that impair a fear memory expression - during the reactivation session, and tested the hypothesis that this disruptive effect relies on a reconsolidation process. Rats previously trained in the contextual fear conditioning (CFC) were reactivated in the presence or absence of a distractor stimulus. In the test, groups reactivated in the original context with distractor displayed a reduction of the freezing response lasting up to 20 days. To check for the involvement of destabilization / reconsolidation mechanisms, we studied the effect of systemic nimodipine (a L-VGCC blocker) or intra-CA1 ifenprodil (a selective GluN2B/NMDAR antagonist) infused right before the reactivation session. Both treatments were able to prevent the disruptive effect of distraction. Ifenprodil results also bolstered the case for hippocampus as the putative brain structure hosting this phenomenon. Our results provide some evidence in support of a behavioral, non-invasive procedure that was able to disrupt an aversive memory in a long-lasting way

Resilience and Vulnerability to Trauma: Early Life Interventions Modulate Aversive Memory Reconsolidation in the Dorsal Hippocampus

Early life experiences program lifelong responses to stress. In agreement, resilience and vulnerability to psychopathologies, such as posttraumatic stress disorder (PTSD), have been suggested to depend on the early background. New therapies have targeted memory reconsolidation as a strategy to modify the emotional valence of traumatic memories. Here, we used animal models to study the molecular mechanism through which early experiences may later affect aversive memory reconsolidation. Handling (H)—separation of pups from dams for 10 min—or maternal separation (MS) — 3-h separation—were performed from PDN1–10, using non-handled (NH) litters as controls. Adult males were trained in a contextual fear conditioning (CFC) task; 24 h later, a short reactivation session was conducted in the conditioned or in a novel context, followed by administration of midazolam 3 mg/kg i.p. (mdz), known to disturb reconsolidation, or vehicle; a test session was performed 24 h after. The immunocontent of relevant proteins was studied 15 and 60 min after memory reactivation in the dorsal hippocampus (dHc) and basolateral amygdala complex (BLA). Mdz-treated controls (NH) showed decreased freezing to the conditioned context, consistent with reconsolidation impairment, but H and MS were resistant to labilization. Additionally, MS males showed increased freezing to the novel context, suggesting fear generalization; H rats showed lower freezing than the other groups, in accordance with previous suggestions of reduced emotionality facing adversities. Increased levels of Zif268, GluN2B, β-actin and polyubiquitination found in the BLA of all groups suggest that memory reconsolidation was triggered. In the dHc, only NH showed increased Zif268 levels after memory retrieval; also, a delay in ERK1/2 activation was found in H and MS animals. We showed here that reconsolidation of a contextual fear memory is insensitive to interference by a GABAergic drug in adult male rats exposed to different neonatal experiences; surprisingly, we found no differences in the reconsolidation process in the BLA, but the dHc appears to suffer temporal desynchronization in the engagement of reconsolidation. Our results support a hippocampal-dependent mechanism for reconsolidation resistance in models of early experiences, which aligns with current hypotheses for the etiology of PTSD

Astrobiology: Water and Life in the Solar System and beyond

After some methodological considerations and a brief historical background (SETI), we describe the three main impulses to the present discipline of exo / astrobiology - extremophyles, the discovery of exoplanets, and the data gathered by several unmanned probes in the solar system. An overview of recent findings concerning the presence of frozen or liquid water in our planetary system is presented, and the main trends for the following years, summarized