Reconsolidation allows fear memory to be updated to a less aversive level through the incorporation of appetitive information.
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ABSTRACT:
SUBMITTER: Haubrich J
PROVIDER: S-EPMC4443944 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The reactivation of a memory through retrieval can render it subject to disruption or modification through the process of memory reconsolidation. In both humans and rodents, briefly reactivating a fear memory results in effective erasure by subsequent extinction training. Here we show that a similar strategy is equally effective in the disruption of appetitive pavlovian cue-food memories. However, systemic administration of the NMDA receptor partial agonist D-cycloserine, under the same behavioural conditions, did not potentiate appetitive memory extinction, suggesting that reactivation does not enhance subsequent extinction learning. To confirm that reactivation followed by extinction reflects a behavioural analogue of memory reconsolidation, we show that prevention of contextual fear memory reactivation by the L-type voltage-gated calcium channel blocker nimodipine interferes with the amnestic outcome. Therefore, the reconsolidation process can be manipulated behaviourally to disrupt both aversive and appetitive memories.
| S-EPMC3516828 | biostudies-literature
Project description:Memory retrieval is considered to have roles in memory enhancement. Recently, memory reconsolidation was suggested to reinforce or integrate new information into reactivated memory. Here, we show that reactivated inhibitory avoidance (IA) memory is enhanced through reconsolidation under conditions in which memory extinction is not induced. This memory enhancement is mediated by neurons in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) through the simultaneous activation of calcineurin-induced proteasome-dependent protein degradation and cAMP responsive element binding protein-mediated gene expression. Interestingly, the amygdala is required for memory reconsolidation and enhancement, whereas the hippocampus and mPFC are required for only memory enhancement. Furthermore, memory enhancement triggered by retrieval utilizes distinct mechanisms to strengthen IA memory by additional learning that depends only on the amygdala. Our findings indicate that reconsolidation functions to strengthen the original memory and show the dynamic nature of reactivated memory through protein degradation and gene expression in multiple brain regions.DOI: http://dx.doi.org/10.7554/eLife.02736.001.
| S-EPMC4067750 | biostudies-literature
Project description:Memories are a product of the concerted activity of many brain areas. Deregulation of consolidation and reprocessing of mnemonic traces that encode fearful experiences might result in fear-related psychopathologies. Here, we assessed how pre-established memories change with experience, particularly the labilization/reconsolidation of memory, using the whole-brain analysis technique of positron emission tomography in male mice. We found differences in glucose consumption in the lateral neocortex, hippocampus and amygdala in mice that underwent labilization/reconsolidation processes compared to animals that did not reactivate a fear memory. We used chemogenetics to obtain insight into the role of cortical areas in these phases of memory and found that the lateral neocortex is necessary for fear memory reconsolidation. Inhibition of lateral neocortex during reconsolidation altered glucose consumption levels in the amygdala. Using an optogenetic/neuronal recording-based strategy we observed that the lateral neocortex is functionally connected with the amygdala, which, along with retrograde labeling using fluorophore-conjugated cholera toxin subunit B, support a monosynaptic connection between these areas and poses this connection as a hot-spot in the circuits involved in reactivation of fear memories.
| S-EPMC6704072 | biostudies-literature
Project description:Adolescence is a time of intensified emotional experiences, during which anxiety and stress-related disorders peak. The most effective behavioral therapies for treating these disorders share exposure-based techniques as a core component. Exposure-based therapies build on the principles of fear extinction learning and involve desensitizing the individual to cues that trigger anxiety. Yet, recent evidence shows an adolescent-specific diminished capacity to extinguish fear responses, suggesting that adolescents may respond less well to exposure-based therapies than other age groups. Here we demonstrate an alternative method for blocking the recall of fear memories in adolescents, building on principles of memory reconsolidation in adults. During memory reconsolidation, a memory that is recalled becomes labile during which time it can be updated. Prior research has shown that extinction training during memory reconsolidation attenuates the recovery of fear memory in human adults and in rodents. Using this method, we show attenuation of fear memory in adolescent humans. These findings have significant implications for treating one of the most vulnerable populations to anxiety and stress related disorders - adolescents - by optimizing exposure therapy based on principles of memory reconsolidation.
| S-EPMC4352863 | biostudies-other
Project description:BackgroundDysfunctional fear responses play a central role in many mental disorders. New insights in learning and memory suggest that pharmacological and behavioural interventions during the reconsolidation of reactivated fear memories may increase the efficacy of therapeutic interventions. It has been proposed that interventions applied during reconsolidation may modify the original fear memory, and thus prevent the spontaneous recovery and reinstatement of the fear response.MethodsWe investigated whether pharmacological (propranolol) and behavioural (reappraisal, multisensory stimulation) interventions reduce fear memory, and prevent reinstatement of fear in comparison to a placebo control group. Eighty healthy female subjects underwent a differential fear conditioning procedure with three stimuli (CS). Two of these (CS+) were paired with an electric shock on day 1. On day 2, 20 subjects were pseudo-randomly assigned to either the propranolol or placebo condition, or underwent one of the two behavioural interventions after one of the two CS+ was reactivated. On day 3, all subjects underwent an extinction phase, followed by a reinstatement test. Dependent variables were US expectancy ratings, fear-potentiated startle, and skin conductance response.ResultsDifferential fear responses to the reactivated and non-reactivated CS+ were observed only in the propranolol condition. Here, the non-reactivated CS+ evoked stronger fear-potentiated startle-responses compared to the placebo group. None of the interventions prevented the return of the extinguished fear response after re-exposure to the unconditioned stimulus.ConclusionsOur data are in line with an increasing body of research stating that the occurrence of reconsolidation may be constrained by boundary conditions such as subtle differences in experimental manipulations and instructions. In conclusion, our findings do not support a beneficial effect in using reconsolidation processes to enhance effects of psychotherapeutic interventions. This implies that more research is required before therapeutic interventions may benefit from a combination with reconsolidation processes.
| S-EPMC4990323 | biostudies-literature
Project description:In classical conditioning, an initially neutral stimulus (conditioned stimulus, CS) becomes associated with a biologically salient event (unconditioned stimulus, US), which might be pain (aversive conditioning) or food (appetitive conditioning). After a few associations, the CS is able to initiate either defensive or consummatory responses, respectively. Contrary to aversive conditioning, appetitive conditioning is rarely investigated in humans, although its importance for normal and pathological behaviors (e.g., obesity, addiction) is undeniable. The present study intents to translate animal findings on appetitive conditioning to humans using food as an US. Thirty-three participants were investigated between 8 and 10 am without breakfast in order to assure that they felt hungry. During two acquisition phases, one geometrical shape (avCS+) predicted an aversive US (painful electric shock), another shape (appCS+) predicted an appetitive US (chocolate or salty pretzel according to the participants' preference), and a third shape (CS-) predicted neither US. In a extinction phase, these three shapes plus a novel shape (NEW) were presented again without US delivery. Valence and arousal ratings as well as startle and skin conductance (SCR) responses were collected as learning indices. We found successful aversive and appetitive conditioning. On the one hand, the avCS+ was rated as more negative and more arousing than the CS- and induced startle potentiation and enhanced SCR. On the other hand, the appCS+ was rated more positive than the CS- and induced startle attenuation and larger SCR. In summary, we successfully confirmed animal findings in (hungry) humans by demonstrating appetitive learning and normal aversive learning.
| S-EPMC4436895 | biostudies-other
Project description:Remembrances of traumata range among the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that in mice successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes as revealed by whole genome RNA sequencing, which is accompanied by higher metabolic, synaptic and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata. 3 biological replicates per group were analyzed. The material analyzed was whole hippocampi from one brain hemisphere, from which total RNA was extracted.
2014-01-04 | E-GEOD-53794 | biostudies-arrayexpress
Project description:Remembrances of traumata range among the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that in mice successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes as revealed by whole genome RNA sequencing, which is accompanied by higher metabolic, synaptic and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata.
2014-01-04 | GSE53794 | GEO
Project description:Traumatic events generate some of the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that, in mice, successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that, whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes, which is accompanied by higher metabolic, synaptic, and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata.
| S-EPMC3986862 | biostudies-literature
Project description:BackgroundIn insect classical conditioning, octopamine (the invertebrate counterpart of noradrenaline) or dopamine has been suggested to mediate reinforcing properties of appetitive or aversive unconditioned stimulus, respectively. However, the roles of octopaminergic and dopaminergic neurons in memory recall have remained unclear.ResultsWe studied the roles of octopaminergic and dopaminergic neurons in appetitive and aversive memory recall in olfactory and visual conditioning in crickets. We found that pharmacological blockade of octopamine and dopamine receptors impaired aversive memory recall and appetitive memory recall, respectively, thereby suggesting that activation of octopaminergic and dopaminergic neurons and the resulting release of octopamine and dopamine are needed for appetitive and aversive memory recall, respectively. On the basis of this finding, we propose a new model in which it is assumed that two types of synaptic connections are formed by conditioning and are activated during memory recall, one type being connections from neurons representing conditioned stimulus to neurons inducing conditioned response and the other being connections from neurons representing conditioned stimulus to octopaminergic or dopaminergic neurons representing appetitive or aversive unconditioned stimulus, respectively. The former is called 'stimulus-response connection' and the latter is called 'stimulus-stimulus connection' by theorists studying classical conditioning in higher vertebrates. Our model predicts that pharmacological blockade of octopamine or dopamine receptors during the first stage of second-order conditioning does not impair second-order conditioning, because it impairs the formation of the stimulus-response connection but not the stimulus-stimulus connection. The results of our study with a cross-modal second-order conditioning were in full accordance with this prediction.ConclusionWe suggest that insect classical conditioning involves the formation of two kinds of memory traces, which match to stimulus-stimulus connection and stimulus-response connection. This is the first study to suggest that classical conditioning in insects involves, as does classical conditioning in higher vertebrates, the formation of stimulus-stimulus connection and its activation for memory recall, which are often called cognitive processes.
| S-EPMC2729297 | biostudies-literature