Retrieval induces hippocampal-dependent reconsolidation of spatial memory

Nonreinforced retrieval can cause extinction and/or reconsolidation, two processes that affect subsequent retrieval in opposite ways. Using the Morris water maze task we show that, in the rat, repeated nonreinforced expression of spatial memory causes extinction, which is unaffected by inhibition of protein synthesis within the CA1 region of the dorsal hippocampus. However, if the number of nonreinforced retrieval trials is insufficient to induce long-lasting extinction, then a hippocampal protein synthesis-dependent reconsolidation process recovers the original memory. Inhibition of hippocampal protein synthesis after reversal learning sessions impairs retention of the reversed preference and blocks persistence of the original one, suggesting that reversal learning involves reconsolidation rather than extinction of the original memory. Our results suggest the existence of a hippocampal protein synthesis-dependent reconsolidation process that operates to recover or update retrieval-weakened memories from incomplete extinction.     

On the role of hippocampal protein synthesis in the consolidation and reconsolidation of object recognition memory

Upon retrieval, consolidated memories are again rendered vulnerable to the action of metabolic blockers, notably protein synthesis inhibitors. This has led to the hypothesis that memories are reconsolidated at the time of retrieval, and that this depends on protein synthesis. Ample evidence indicates that the hippocampus plays a key role both in the consolidation and reconsolidation of different memories. Despite this fact, at present there are no studies about the consequences of hippocampal protein synthesis inhibition in the storage and post-retrieval persistence of object recognition memory. Here we report that infusion of the protein synthesis inhibitor anisomycin in the dorsal CA1 region immediately or 180 min but not 360 min after training impairs consolidation of long-term object recognition memory without affecting short-term memory, exploratory behavior, anxiety state, or hippocampal functionality. When given into CA1 after memory reactivation in the presence of familiar objects, ANI did not affect further retention. However, when administered into CA1 immediately after exposing animals to a novel and a familiar object, ANI impaired memory of both of them. The amnesic effect of ANI was long-lasting, did not happen after exposure to two novel objects, following exploration of the context alone, or in the absence of specific stimuli, suggesting that it was not reversible but was contingent on the reactivation of the consolidated trace in the presence of a salient, behaviorally relevant novel cue. Our results indicate that hippocampal protein synthesis is required during a limited post-training time window for consolidation of object recognition memory and show that the hippocampus is engaged during reconsolidation of this type of memory, maybe accruing new information into the original trace.     

The allocation of valenced concepts onto 3D space

The valence–space metaphor research area investigates the metaphorical mapping of valenced concepts onto space. Research findings from this area indicate that positive, neutral, and negative concepts are associated with upward, midward, and downward locations, respectively, in the vertical plane. The same research area has also indicated that such concepts seem to have no preferential location on the horizontal plane. The approach–avoidance effect consists in decreasing the distance between positive stimuli and the body (i.e. approach) and increasing the distance between negative stimuli and the body (i.e. avoid). Thus, the valence–space metaphor accounts for the mapping of valenced concepts onto the vertical and horizontal planes, and the approach–avoidance effect accounts for the mapping of valenced concepts onto the “depth” plane. By using a cube conceived for the study of allocation of valenced concepts onto 3D space, we show in three studies that positive concepts are placed in upward locations and near the participants’ body, negative concepts are placed in downward locations and far from the participants’ body, and neutral concepts are placed in between these concepts in both planes.     

Acceptance of chronic pain in fibromyalgia patients: adaptation of Chronic Pain Acceptance Questionnaire (CPAQ) in a Spanish population

Acceptance of chronic pain appears as an important factor in the personal ability to restore functioning in the presence of chronic pain. The Chronic Pain Acceptance Questionnaire (CPAQ) is currently the only instrument used to assess the acceptance of pain in people who suffer chronic pain. The revised 20-item version of McCracken and cols. (2004) showed satisfactory psychometric properties. Nevertheless, the CPAQ has not been used in Spain in fibromyalgia patients. The first goal of the study is to examine the Spanish translation of the CPAQ and assess its psychometric properties in a sample of 145 subjects with a diagnosis of fibromyalgia. The second purpose was to analyze the relationships between the CPAQ and other important measures of pain adjustment. Results of exploratory factor analysis indicated that the two-factor model, in a 15-item test, provided a good fit to the data in fibromyalgia patients. Regression analyses showed strong relations with criteria variables (pain intensity, anxiety, depression, etc.) though the subscale Activity Engagement contributed more than Pain Willingness to the prediction of criteria variables.     

Counterfactual Evaluation of Outcomes in Social Risk Decision-Making Situations: The Cognitive Developmental Paradox Revisited

We report a study that examined the existence of a cognitive developmental paradox in the counterfactual evaluation of decision-making outcomes. According to this paradox adolescents and young adults could be able to apply counterfactual reasoning and, yet, their counterfactual evaluation of outcomes could be biased in a salient socio-emotional context. To this aim, we analyzed the impact of health and social feedback on the counterfactual evaluation of outcomes in a laboratory decision-making task involving short narratives with the presence of peers. Forty risky (e.g., taking or refusing a drug), forty neutral decisions (e.g., eating a hamburger or a hotdog), and emotions felt following positive or negative outcomes were examined in 256 early, mid- and late adolescents, and young adults, evenly distributed. Results showed that emotional ratings to negative outcomes (regret and disappointment) but not to positive outcomes (relief and elation) were attenuated when feedback was provided. Evidence of development of cognitive decision-making capacities did also exist, as the capacity to perform faster emotional ratings and to differentially allocate more resources to the elaboration of emotional ratings when no feedback information was available increased with age. Overall, we interpret these findings as challenging the traditional cognitive developmental assumption that development necessarily proceeds from lesser to greater capacities, reflecting the impact of socio-emotional processes that could bias the counterfactual evaluation of social decision-making outcomes.     

On the requirement of nitric oxide signaling in the amygdala for consolidation of inhibitory avoidance memory

Evidence suggests that the NO/sGC/PKG pathway plays a key role in memory processing but the actual participation of this signaling cascade in the amygdala during memory consolidation remains unknown. Here, we show that when infused in the amygdala immediately after inhibitory avoidance training, but not later, the NO synthase inhibitor L-NNA hindered long-term memory retention without affecting locomotion, exploratory behavior, anxiety state or retrieval of the avoidance response. The amnesic effect of L-NNA was not state-dependent and was mimicked by the soluble guanylyl cyclase inhibitor LY83583 and the PKG inhibitor KT-5823. On the contrary, post-training intra-amygdala infusion of the NOS substrate L-Arg, the NO-releasing compound SNAP or the non-hydrolysable analog of cGMP 8Br-cGMP increased memory retention in a dose-dependent manner. Co-infusion of 8Br-cGMP reversed the amnesic effect of L-NNA and LY83583 but not that of KT-5823. Our data indicate that the NO-induced activation of PKG in the amygdala is a necessary step for consolidation of inhibitory avoidance memory.     

Retrieval does not induce reconsolidation of inhibitory avoidance memory

It has been suggested that retrieval during a nonreinforced test induces reconsolidation instead of extinction of the mnemonic trace. Reconsolidation would preserve the original memory from the labilization induced by its nonreinforced recall through a hitherto uncharacterized mechanism requiring protein synthesis. Given the importance that such a process would have in terms of maintaining, as part of the animal behavioral repertoire, a learned response that has been devalued by experience, we analyzed its existence for the memory associated with a one-trial, step-down inhibitory avoidance task (IA), a memory whose consolidation and extinction require protein synthesis in the CA1 region of the dorsal hippocampus (CA1) and involve the participation of the basolateral amygdala (BLA) and entorhinal cortex (ENT). Rats were trained in IA, and 24 h later they were submitted either to a pure reactivation session (retrieval without stepping down), which was unable by itself to initiate extinction of the avoidance response, or to a second training session. Fifteen minutes before or 3 h after either the reactivation or the retraining sessions, animals were infused with the protein synthesis inhibitor anisomycin (ANI) into CA1, BLA, or ENT. Contrary to the prediction of the reconsolidation hypothesis, none of these treatments affected subsequent memory retention. Because reconsolidation is regarded to be a direct consequence of retrieval, one would expect that, when given before a retention test or a pure reactivation session, enhancers of memory expression should permanently improve retention and, therefore, facilitate retrieval both in that and in subsequent sessions. Using two well-known retrieval enhancers, noradrenaline and adrenocorticotropin(1-24), we could not find any evidence suggestive of reconsolidation. Hence, our results indicate that there is no retrieval-induced, protein synthesis-dependent process that would cause reconsolidation of IA memory.     

Different time course for the memory facilitating effect of bicuculline in hippocampus, entorhinal cortex, and posterior parietal cortex of rats

Several lines of evidence indicate that gamma-aminobutyric acid (GABA) type A (GABA(A)) receptors regulate memory consolidation. Here we studied the effect on consolidation of the selective antagonist of GABA(A) receptors, bicuculline, given into several regions of the cortex at different times after one-trial step-down inhibitory avoidance (0.5 mA, 2-s footshock). Rats were bilaterally implanted with cannulae aimed at the CA1 region of the dorsal hippocampus, entorhinal cortex or posterior parietal cortex, three areas known to be involved in the memory consolidation of this task. At different times after training, bicuculline (0.5 microg/side) was infused into the above mentioned structures. Bicuculline increased memory retention when administered either immediately or 1.5h after training into CA1, and both immediately and 3h after training in the entorhinal or parietal cortex. Thus, in agreement with previous findings using other drugs, the response was biphasic in these latter structures. This suggests that GABAergic mechanisms normally downregulate, memory processing by inhibiting on-going activities necessary for consolidation at the times in which bicuculline was effective in each structure. Based on previous findings, in the hippocampus, such activity involves a number of receptors and signaling pathways in the first 1.5h after training. In the entorhinal and parietal cortex memory-related activities include the participation of protein kinase A and extracellularly regulated kinase (ERK) twice, right after training and then again 3h later.