Post-weaning housing conditions influence freezing during contextual fear conditioning in adult rats

The present study aimed to investigate the influence of housing conditions on contextual fear memory malleability. Male Wistar rats were housed in enriched, standard, or impoverished conditions after weaning and remained in these conditions throughout the entire experiment. After six weeks into those housing conditions, all animals underwent a 3-day protocol including contextual fear conditioning (day 1), memory reactivation followed by systemic administration of midazolam or vehicle (day 2), and a retention test (day 3). Percentage freezing was used as a behavioral measure of contextual fear. There was no evidence for an effect of housing conditions on the sensitivity of contextual fear memory to amnestic effects of post-reactivation midazolam administration, and no indication for amnestic effects of post-reactivation midazolam overall (including in the standard group). The inability to replicate previous demonstrations of post-reactivation amnesia using the same protocol underscores the subtle nature of post-reactivation pharmacological memory interference. Notably, impoverished housing resulted in a decrease in contextual freezing during contextual fear conditioning, reactivation and retention testing, compared to enriched and standard housing conditions. This observation warrants caution when interpreting the results from experiments regarding effects of housing on fear memory processes, particularly when freezing is used as a measure of fear.Fil: Schroyens, Natalie. Katholikie Universiteit Leuven; BélgicaFil: Bender, Crhistian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Alfei Palloni, Joaquin Matías. Katholikie Universiteit Leuven; BélgicaFil: Molina, Víctor Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Luyten, Laura. Katholikie Universiteit Leuven; BélgicaFil: Beckers, Tom. Katholikie Universiteit Leuven; Bélgic

Prediction error and trace dominance determine the fate of fear memories after post-training manipulations

Different mnemonic outcomes have been observed when associative memories are reactivated by CS exposure and followed by amnestics. These outcomes include mere retrieval, destabilization- reconsolidation, a transitional period (which is insensitive to amnestics), and extinction learning. However, little is known about the interaction between initial learning conditions and these outcomes during a reinforced or nonreinforced reactivation. Here we systematically combined temporally specific memories with different reactivation parameters to observe whether these four outcomes are determined by the conditions established during training. First, we validated two training regimens with different temporal expectations about US arrival. Then, using Midazolam (MDZ) as an amnestic agent, fear memories in both learning conditions were submitted to retraining either under identical or different parameters to the original training. Destabilization (i.e., susceptibly to MDZ) occurred when reactivation was reinforced, provided the occurrence of a temporal prediction error about US arrival. In subsequent experiments, both treatments were systematically reactivated by nonreinforced context exposure of different lengths, which allowed to explore the interaction between training and reactivation lengths. These results suggest that temporal prediction error and trace dominance determine the extent to which reactivation produces the different outcomes.Fil: Alfei Palloni, Joaquin Matías. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferrer Monti, Roque Ignacio. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Molina, Victor Alejandro. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bueno, Adrián Marcelo. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Urcelay, Gonzalo Pablo. University of Cambridge; Reino Unid

An appetitive experience after fear memory destabilization attenuates fear retention: Involvement GluN2B-NMDA receptors in the basolateral amygdala complex

It is known that a consolidated memory can return to a labile state and become transiently malleable following reactivation. This instability is followed by a restabilization phase termed reconsolidation. In this work, we explored whether an unrelated appetitive experience (voluntary consumption of diluted sucrose) can affect a contextual fear memory in rats during the reactivation-induced destabilization phase. Our findings show that exposure to an appetitive experience following reactivation can diminish fear retention. This effect persisted after 1 wk. Importantly, it was achieved only under conditions that induced fear memory destabilization. This result could not be explained as a potentiated extinction, because sucrose was unable to promote extinction. Since GluN2B-containing NMDA receptors in the basolateral amygdala complex (BLA) have been implicated in triggering fear memory destabilization, we decided to block pharmacologically these receptors to explore the neurobiological bases of the observed effect. Intra-BLA infusion with ifenprodil, a GluN2B-NMDA antagonist, prevented the fear reduction caused by the appetitive experience. In sum, these results suggest that the expression of a fear memory can be dampened by an unrelated appetitive experience, as long as memory destabilization is achieved during reactivation. Possible mechanisms behind this effect and its clinical implications are discussed.Fil: Ferrer Monti, Roque Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudio sobre Cultura y Sociedad. Centro de Investigaciones de la Facultad de Psicología - Grupo Vinculado CIPSI; ArgentinaFil: Giachero, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Alfei Palloni, Joaquin Matías. Katholikie Universiteit Leuven; BélgicaFil: Bueno, Adrián Marcelo. Universidad Nacional de Córdoba; ArgentinaFil: Cuadra, Gabriel R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Molina, Víctor Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; Argentin