Memory Integration as a Challenge to the Consolidation/Reconsolidation Hypothesis: Similarities, Differences and Perspectives

We recently proposed that retrograde amnesia does not result from a disruption of the consolidation/reconsolidation processes but rather to the integration of the internal state induced by the amnesic treatment within the initial memory. Accordingly, the performance disruption induced by an amnesic agent does not result from a disruption of the memory fixation process, but from a difference in the internal state present during the learning phase (or reactivation) and at the later retention test: a case of state-dependency. In the present article, we will review similarities and differences these two competing views may have on memory processing. We will also consider the consequences the integration concept may have on the way memory is built, maintained and retrieved, as well as future research perspectives that such a new view may generate

Post Traumatic Stress Disorder and Substance Use Disorder as Two Pathologies Affecting Memory Reactivation: Implications for New Therapeutic Approaches

In the present review, we provide evidence indicating that although post traumatic stress disorder (PTSD) and substance use disorder (SUD) are two distinct pathologies with very different impacts on people affected by these chronic illnesses, they share numerous common characteristics, present high rates of co-morbidity, and may result from common physiological dysfunctions. We propose that these pathologies result from hyper reactivity to reminders, and thus should be considered as two disorders of memory, treated as such. We review the different possibilities to intervene on pathological memories such as extinction therapy and reconsolidation blockade. We also introduce new therapeutic avenues directly indicate by our recent proposal to replace the consolidation/reconsolidation hypothesis by the integration concept. State dependency and emotional remodeling are two innovative treatments that have already provided encouraging results. In summary, this review shows that the discovery of reactivation-dependent memory malleability has open new therapeutic avenues based on the reprocessing of pathological memories, which constitute promising approaches to treat PTSD and SUD

PIXSIC: A Wireless Intracerebral Radiosensitive Probe in Freely Moving Rats

International audienceThe aim of this study was to demonstrate the potential of a wireless pixelated β+-sensitive intracerebral probe (PIXSIC) for in vivo positron emission tomographic (PET) radiopharmacology in awake and freely moving rodents. The binding of [ 11 C]raclopride to D 2 dopamine receptors was measured in anesthetized and awake rats following injection of the radiotracer. Competitive binding was assessed with a cold raclopride injection 20 minutes later. The device can accurately monitor binding of PET ligands in freely moving rodents with a high spatiotemporal resolution. Reproducible time-activity curves were obtained for pixels throughout the striatum and cerebellum. A significantly lower [ 11 C]raclopride tracer–specific binding was observed in awake animals. These first results pave the way for PET tracer pharmacokinetics measurements in freely moving rodents

Is drug addiction due to hypersensitivity to environmental cues? A possible model for Psychiatric pathologies of out range memories. In Endophenotypes of psychiatric and neurodegenerative disorders in animal models.

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The differential involvement of the prelimbic and infralimbic cortices in response conflict affects behavioral flexibility in rats trained in a new automated strategy-switching task.

International audienceTo assess the role of the prelimbic (PL) and infralimbic (IL) cortices in mediating strategy switching, rats were trained in a new automated task in a Y-maze allowing a careful analysis of rats' behavior. In this situation, rats can only use two egocentric (Right, Left) and two visual (Light, Dark) strategies. In the first experiment, rats with PL, IL, or PL/IL lesions were compared with sham-operated rats when trained to reach a criterion of 10 consecutive correct responses with a light strategy before being trained with a response strategy (rule shifting), and finally with the reversed response strategy (reversal). In the second experiment, sham-operated and PL-lesioned rats had their first two strategy switches in the reverse order, which was followed by a second rule shifting and reversal. The results indicate that lesions did not affect initial acquisition, but impaired the first rule shifting and reversal. Thorough analyses of rats' performance indicate that lesioned rats were still able to demonstrate some behavioral flexibility but have difficulties in solving response conflicts, which in turn may affect behavioral flexibility. Both areas were differentially involved in the resolution of response conflict, with the IL involved in the choice of strategy previously known to be nonvalid, and the PL in the selection and maintenance of that strategy

Comparing integration and contextual binding accounts of memory impairment

International audienceIn their recent Opinion (A contextual binding theory of episodic memory: systems consolidation reconsidered. Nat. Rev. Neurosci. 20, 364–375 (2019)), Yonelinas et al. reconsidered the standard systems consolidation theory (SSCT) and proposed the contextual binding theory (CBT). For these authors, the long-term development of memory and forgetting can be explained by the way information has been bound during memory formation. Information will be forgotten because different material that occurs in the same context interferes with the item to be learned. The authors propose that CBT can explain better than the SSCT several forgetting effects, including interference effects and retrograde amnesia after post-training hippocampal lesions.We were pleased to see that this CBT view has much in common with our own ‘integration concept’ (IC), which we introduced to challenge the consolidation–reconsolidation hypothesis. According to the IC, memories, when in an active state (after training or reactivation), become malleable and integrate new information that is present. Depending on the information available at that time, memories can be updated, strengthened (by coherent information), disrupted (by incoherent information resulting from, for example, amnesic treatments or interference) or greatly altered (false memory). We have described evidence showing that performance disruption due to post-training amnesic treatments mainly results from impairments in retrieval that are induced by contextual differences between training and testing.There are clear convergences between CBT and the IC model. Both accounts challenge the long-held consolidation hypotheses and emphasize a prominent role of environmental context (internal and external) as a major determinant of forgetting. Both accounts note that contextual information presented just before or just after the study event have similar effects on memory, a concept consistent with recent findings.However, some essential differences should also be noted. Although both IC and CBT claim to explain temporally graded retrograde amnesia, they do not address the same consolidation processes. IC proposes to explain retrograde amnesia resulting from amnesic treatments delivered during the first minutes following training and thus affecting presumed consolidation–reconsolidation processes. By contrast, CBT suggests an explanation for retrograde amnesia resulting from hippocampal lesions administered days to weeks after training, therefore concerning standard systems consolidation.Another principal difference between the two frameworks concerns the origin of memory impairment. For CBT, the main source of forgetting is interference between memories that share similar context or content during memory formation. The IC account proposes that forgetting results from a contextual mismatch between acquisition and testing, inducing retrieval difficulties10. In agreement with the IC, active memories are malleable and integrate any contextual information present. Accordingly, interference is only one source of disruption, among others. As a consequence, the IC model can account for various performance modulations, such as anterograde and retrograde amnesia5,6, interference, false memories, as well as counterconditioning and promnesic effects.Interestingly, the recent literature seems to converge towards the same aim: revisiting serious shortcomings of older theories of memory impairment. By doing that, CBT and IC both serve to stimulate new conceptions of memory

Rôle fonctionnel des aires prélimbique et infralimbique du cortex préfrontal médian (une implication dans la résolution de conflits ?)

Les aires prélimbique (PL) et infralimbique (IL) du cortex préfrontal médian (CPFm) du rat sont impliquées dans de nombreux processus cognitifs. Le but de ma thèse est de déterminer s il existe une fonction supra-modalitaire pouvant rendre compte de l ensemble des données de la littérature. Pour cela, l effet de dysfonctionnements des cortex PL ou/et IL (lésion, inactivation, blocage des récepteurs dopaminergique D1) a été étudié dans une nouvelle épreuve automatisée de changements de stratégie et dans l extinction d une peur conditionnée. Les lésions du CPFm perturbent changements de règles et renversements. L analyse fine du comportement indique que les lésions du CPFm perturbent l adoption d une stratégie en conflit avec un apprentissage antérieur, l IL étant impliqué dans le choix initial de cette stratégie et le PL dans son maintien. L injection locale d un antagoniste D1 et l inactivation du PL conduisent à des résultats différents semblant résulter de dérégulations locales et à distance. Les lésions PL/IL retardent l extinction d une peur conditionnée lorsque le stimulus conditionnel est ambigu, c'est-à-dire lorsque l extinction a lieu dans un contexte différent de celui du conditionnement et lorsque l association initiale est réactivée par restauration de la peur. Nos données indiquent que le CPFm joue un rôle dans les processus d interférence proactive. Sur la base de ce travail et de l examen de la littérature, nous proposons que les aires PL/IL soient impliquées dans la résolution de conflits, l incidence sur d autres processus, comme la flexibilité comportementale, pouvant n être que la conséquence de ce déficit.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Prelimbic cortex specific lesions disrupt delayed-variable response tasks in the rat.

International audienceThe role of the prelimbic cortex (PL) in rats was investigated with excitotoxic lesions. PL lesions altered the alternation scores in spontaneous and reinforced spatial delayed-alternation tasks. PL lesions induced a delay in conditioning under a temporal go/no-go alternation schedule but not under a continuous food-reinforcement schedule in a runway. PL lesions had no effect on the acquisition of a standard radial-arm-maze task nor on a fixed-goal location task but disrupted the acquisition of a variable-goal location task in a radial-arm maze. The present results indicate that PL lesions replicated most of the behavioral deficits obtained with larger prefrontal lesions. PL lesions disrupted the acquisition of delayed-variable response tasks while leaving unaffected fixed-response tasks. These results are discussed in relation with a working-memory, a response-selection, and an attentional hypothesis