The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Jorge Alberto Quillfeldt - One of the best experts on this subject based on the ideXlab platform.
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Time-course of Systems Consolidation and fear memory generalization in adolescent rats of different sex
2020Co-Authors: Ana P. Crestani, Lucas De Oliveira Alvares, Fernanda N. Lotz, Mirelle Araujo Casagrande, Bruno Popik, Ketlyn Talise Knak Guerra, Jorge Alberto QuillfeldtAbstract:Systems Consolidation is a time-dependent process in which the retrieval of contextual memories becomes progressively independent from the hippocampus and more reliant on cortical structures. One qualitative consequence, supposed to be causally related, is the progressive loss of memory precision. Memory generalization, however, is a much more complex phenomena, and may take place much faster in adult animals, for instance, in response to changes in the available levels of sex hormones. In this sense, females are known to display a generalized memory earlier than males. Sex differences might have an important role in the modulation of mnemonic processes, and despite being of paramount importance for the understanding of the cognitive dynamics of juveniles, it remains poorly investigated. Here, we studied adolescent rats (P42-49) of different sex comparing the natural time-course of Systems Consolidation as verified both by the hippocampus-dependency and the onset of memory generalization. Contextual fear discrimination was quantified at different time-points after learning (2, 7, 14, 21 and 28 days). Our results demonstrated that, contrary to what is observed in adults, memory generalization occurs earlier in adolescent males (14 days) than in females (28 days). During adolescence, females display a higher mean discrimination index at all time-points, suggesting that they retain a more detailed memory. Likewise, pre-test pharmacological inactivation of the hippocampus (with GABAA agonist muscimol) was able to impair memory retrieval in females, but not in males, 14 days after training. These results support a causal relationship between memory generalization and retrieval independence from the hippocampus in male adolescent rats. However, both aspects of the Systems Consolidation process appear to be distinctly modulated in animals of different sex, with males (and ovariectomized females) enduring an accelerated onset of both memory precision loss and the hippocampus independence compared to females, suggesting a clear role for gonadal hormones in this cognitive corticalization process.
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Temporal Flexibility of Systems Consolidation and the Synaptic Occupancy/Reset Theory (SORT): Cues About the Nature of the Engram
Frontiers in synaptic neuroscience, 2019Co-Authors: Jorge Alberto QuillfeldtAbstract: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 sucession 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 prolonguing 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.
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temporal flexibility of Systems Consolidation and the synaptic occupancy reset theory sort cues about the nature of the engram
Frontiers in Synaptic Neuroscience, 2019Co-Authors: Jorge Alberto QuillfeldtAbstract: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 sucession 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 prolonguing 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.
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ReConsolidation-induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens.
Hippocampus, 2017Co-Authors: Rodrigo O. Sierra, Lizeth K. Pedraza, Ana Paula Crestani, Lucas De Oliveira Alvares, Josué Haubrich, Fabiana Santana, Flávia Z. Boos, Querusche Klippel Zanona, Maria Elisa Calcagnotto, Jorge Alberto QuillfeldtAbstract:Systems Consolidation is a time-dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization-dependent mechanism interpreted as reConsolidation, that restored the normal course of Systems Consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation-induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1-anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying Systems Consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reConsolidation-driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of Systems Consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.
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Sequential learning during contextual fear conditioning guides the rate of Systems Consolidation: Implications for Consolidation of multiple memory traces.
Hippocampus, 2017Co-Authors: Lizeth K. Pedraza, Jorge Alberto Quillfeldt, Rodrigo O. Sierra, Ana Paula Crestani, Lucas De Oliveira AlvaresAbstract:Systems Consolidation has been described as a time-dependent reorganization process involving the neocortical and hippocampal networks underlying memory storage and retrieval. Previous studies of our lab were able to demonstrate that Systems Consolidation is a dynamic process, rather than a merely passive, time-dependent phenomenon. Here, we studied the influence of sequential learning in contextual fear conditioning (CFC) with different training intensities in the time-course of hippocampal dependency and contextual specificity. We found that sequential learning with high-intensity shocks during CFC induces generalization of the first learning (context A) and maintains contextual specificity of the second learning (context B) 15 days after acquisition. Moreover, subsequent experiences reorganize brain structures involved in retrieval, accelerating the involvement of cortical structures and diminishing the hippocampal participation. Exposure to original context before novelty seems to only induce context specificity in hippocampal-dependent memories. We propose that Systems Consolidation could be considered a potential biological mechanism for reducing possible interferences between similar memory traces. © 2017 Wiley Periodicals, Inc.
Karim Nader - One of the best experts on this subject based on the ideXlab platform.
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differential role of the anterior and intralaminar lateral thalamic nuclei in Systems Consolidation and reConsolidation
Brain Structure & Function, 2018Co-Authors: Joëlle Lopez, Karine Gamache, Carmelo Milo, Karim NaderAbstract:The anterior thalamic nuclei (ATN) and the intralaminar/lateral thalamic nuclei (ILN/LT) play different roles in memory processes. The ATN are believed to be part of an extended hippocampal system, and the ILN/LT have strong connections with the medial prefrontal cortex. It was shown that the ILN/LT are involved in Systems Consolidation. However, whether they are necessary for memory retrieval as well remains unclear. We, therefore, used c-Fos immunohistochemistry and reversible inactivations to investigate the role of the ATN and ILN/LT in recent and remote contextual fear memory retrieval in rats. The results confirm a differential role of the ATN and ILN/LT in Systems Consolidation, showing the involvement of the ATN in recent but not remote memory retrieval. This study also pinpoints which specific nuclei are involved in retrieval: the anterodorsal nucleus for recent memories, and the lateral mediodorsal nucleus for remote memories. Lastly, we also show that the ATN are not involved in reConsolidation. Together, the results suggest that these nuclei provide critical feedback for successful memory retrieval and Systems Consolidation.
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Differential role of the anterior and intralaminar/lateral thalamic nuclei in Systems Consolidation and reConsolidation.
Brain structure & function, 2017Co-Authors: Joëlle Lopez, Karine Gamache, Carmelo Milo, Karim NaderAbstract:The anterior thalamic nuclei (ATN) and the intralaminar/lateral thalamic nuclei (ILN/LT) play different roles in memory processes. The ATN are believed to be part of an extended hippocampal system, and the ILN/LT have strong connections with the medial prefrontal cortex. It was shown that the ILN/LT are involved in Systems Consolidation. However, whether they are necessary for memory retrieval as well remains unclear. We, therefore, used c-Fos immunohistochemistry and reversible inactivations to investigate the role of the ATN and ILN/LT in recent and remote contextual fear memory retrieval in rats. The results confirm a differential role of the ATN and ILN/LT in Systems Consolidation, showing the involvement of the ATN in recent but not remote memory retrieval. This study also pinpoints which specific nuclei are involved in retrieval: the anterodorsal nucleus for recent memories, and the lateral mediodorsal nucleus for remote memories. Lastly, we also show that the ATN are not involved in reConsolidation. Together, the results suggest that these nuclei provide critical feedback for successful memory retrieval and Systems Consolidation.
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Cellular and Systems reConsolidation in the hippocampus.
Neuron, 2002Co-Authors: Jacek Debiec, Joseph E. Ledoux, Karim NaderAbstract:Cellular theories of memory Consolidation posit that new memories require new protein synthesis in order to be stored. Systems Consolidation theories posit that the hippocampus has a time-limited role in memory storage, after which the memory is independent of the hippocampus. Here, we show that intra-hippocampal infusions of the protein synthesis inhibitor anisomycin caused amnesia for a consolidated hippocampal-dependent contextual fear memory, but only if the memory was reactivated prior to infusion. The effect occurred even if reactivation was delayed for 45 days after training, a time when contextual memory is independent of the hippocampus. Indeed, reactivation of a hippocampus-independent memory caused the trace to again become hippocampus dependent, but only for 2 days rather than for weeks. Thus, hippocampal memories can undergo reConsolidation at both the cellular and Systems levels.
Lucas De Oliveira Alvares - One of the best experts on this subject based on the ideXlab platform.
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Time-course of Systems Consolidation and fear memory generalization in adolescent rats of different sex
2020Co-Authors: Ana P. Crestani, Lucas De Oliveira Alvares, Fernanda N. Lotz, Mirelle Araujo Casagrande, Bruno Popik, Ketlyn Talise Knak Guerra, Jorge Alberto QuillfeldtAbstract:Systems Consolidation is a time-dependent process in which the retrieval of contextual memories becomes progressively independent from the hippocampus and more reliant on cortical structures. One qualitative consequence, supposed to be causally related, is the progressive loss of memory precision. Memory generalization, however, is a much more complex phenomena, and may take place much faster in adult animals, for instance, in response to changes in the available levels of sex hormones. In this sense, females are known to display a generalized memory earlier than males. Sex differences might have an important role in the modulation of mnemonic processes, and despite being of paramount importance for the understanding of the cognitive dynamics of juveniles, it remains poorly investigated. Here, we studied adolescent rats (P42-49) of different sex comparing the natural time-course of Systems Consolidation as verified both by the hippocampus-dependency and the onset of memory generalization. Contextual fear discrimination was quantified at different time-points after learning (2, 7, 14, 21 and 28 days). Our results demonstrated that, contrary to what is observed in adults, memory generalization occurs earlier in adolescent males (14 days) than in females (28 days). During adolescence, females display a higher mean discrimination index at all time-points, suggesting that they retain a more detailed memory. Likewise, pre-test pharmacological inactivation of the hippocampus (with GABAA agonist muscimol) was able to impair memory retrieval in females, but not in males, 14 days after training. These results support a causal relationship between memory generalization and retrieval independence from the hippocampus in male adolescent rats. However, both aspects of the Systems Consolidation process appear to be distinctly modulated in animals of different sex, with males (and ovariectomized females) enduring an accelerated onset of both memory precision loss and the hippocampus independence compared to females, suggesting a clear role for gonadal hormones in this cognitive corticalization process.
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Chronic fluoxetine prevents fear memory generalization and enhances subsequent extinction by remodeling hippocampal dendritic spines and slowing down Systems Consolidation.
Translational psychiatry, 2019Co-Authors: Lizeth K. Pedraza, Rodrigo O. Sierra, Fernanda N. Lotz, Marcelo Giachero, Walquiria Nunes-souza, Lucas De Oliveira AlvaresAbstract:Fear memory overgeneralization contributes to the genesis and persistence of anxiety disorders and is a central hallmark in the pathophysiology of post-traumatic stress disorder (PTSD). Recent findings suggest that fear generalization is closely related to hippocampal dependency during retrieval. The selective serotonin reuptake inhibitor (SSRI) fluoxetine has been used as a first-line treatment for PTSD; however, how it exerts its therapeutic effect remains a matter of debate. Here, using contextual fear conditioning in rats, we show that chronic fluoxetine treatment prevents fear generalization and enhances subsequent extinction. Moreover, fluoxetine treatment after extinction prevents spontaneous recovery. The mechanism through which fluoxetine affects generalization and extinction seems to be through the postponement of Systems Consolidation, thereby maintaining hippocampal involvement during retrieval. Such an effect relies on a remodeling of dendritic spines in the hippocampus, as well as the number of mature, mushroom-type spines promoted by fluoxetine treatment. In order to further investigate whether fear generalization is a potential predictor of extinction effectiveness, we categorized a large naive population according to their generalization rate. We found that discriminator rats showed a better extinction profile compared to generalizers, suggesting that the generalization rate predicts extinction effectiveness. Hence, we propose that the therapeutic strategy of choice should take into account the extension of memory generalization, in which therapies based on extinction could induce a better outcome in patients who present less fear overgeneralization. These results open new avenues for the development of interventions that prevent fear generalization by maintaining memory dependency of the hippocampus.
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ReConsolidation-induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens.
Hippocampus, 2017Co-Authors: Rodrigo O. Sierra, Lizeth K. Pedraza, Ana Paula Crestani, Lucas De Oliveira Alvares, Josué Haubrich, Fabiana Santana, Flávia Z. Boos, Querusche Klippel Zanona, Maria Elisa Calcagnotto, Jorge Alberto QuillfeldtAbstract:Systems Consolidation is a time-dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization-dependent mechanism interpreted as reConsolidation, that restored the normal course of Systems Consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation-induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1-anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying Systems Consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reConsolidation-driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of Systems Consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.
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Sequential learning during contextual fear conditioning guides the rate of Systems Consolidation: Implications for Consolidation of multiple memory traces.
Hippocampus, 2017Co-Authors: Lizeth K. Pedraza, Jorge Alberto Quillfeldt, Rodrigo O. Sierra, Ana Paula Crestani, Lucas De Oliveira AlvaresAbstract:Systems Consolidation has been described as a time-dependent reorganization process involving the neocortical and hippocampal networks underlying memory storage and retrieval. Previous studies of our lab were able to demonstrate that Systems Consolidation is a dynamic process, rather than a merely passive, time-dependent phenomenon. Here, we studied the influence of sequential learning in contextual fear conditioning (CFC) with different training intensities in the time-course of hippocampal dependency and contextual specificity. We found that sequential learning with high-intensity shocks during CFC induces generalization of the first learning (context A) and maintains contextual specificity of the second learning (context B) 15 days after acquisition. Moreover, subsequent experiences reorganize brain structures involved in retrieval, accelerating the involvement of cortical structures and diminishing the hippocampal participation. Exposure to original context before novelty seems to only induce context specificity in hippocampal-dependent memories. We propose that Systems Consolidation could be considered a potential biological mechanism for reducing possible interferences between similar memory traces. © 2017 Wiley Periodicals, Inc.
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Novel learning accelerates Systems Consolidation of a contextual fear memory.
Hippocampus, 2016Co-Authors: Josué Haubrich, Lucas De Oliveira Alvares, Lindsey De Freitas Cassini, Felipe Diehl, Fabiana Santana, Lucas Fürstenau De Oliveira, Jorge Alberto QuillfeldtAbstract:After initial encoding memories may undergo a time-dependent reorganization, becoming progressively independent from the hippocampus (HPC) and dependent on cortical regions such as the anterior cingulate cortex (ACC). Although the mechanisms underlying Systems Consolidation are somewhat known, the factors determining its temporal dynamics are still poorly understood. Here, we studied the influence of novel learning occurring between training and test sessions on the time-course of HPC- and ACC-dependency of contextual fear conditioning (CFC) memory expression. We found that muscimol was disruptive when infused into the HPC up to 35 days after training, while the ACC is vulnerable only after 45 days. However, when animals were subjected to a series of additional, distinct tasks to be learned within the first 3 weeks, muscimol became effective sooner. Muscimol had no effect in the HPC at 20 days after training, exactly when the ACC becomes responsive to this treatment. Thus, our data indicates that the encoding of new information generates a tight interplay between distinct memories, accelerating the reorganization of previously stored long term memories between the hippocampal and cortical areas. © 2016 Wiley Periodicals, Inc.
Joëlle Lopez - One of the best experts on this subject based on the ideXlab platform.
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differential role of the anterior and intralaminar lateral thalamic nuclei in Systems Consolidation and reConsolidation
Brain Structure & Function, 2018Co-Authors: Joëlle Lopez, Karine Gamache, Carmelo Milo, Karim NaderAbstract:The anterior thalamic nuclei (ATN) and the intralaminar/lateral thalamic nuclei (ILN/LT) play different roles in memory processes. The ATN are believed to be part of an extended hippocampal system, and the ILN/LT have strong connections with the medial prefrontal cortex. It was shown that the ILN/LT are involved in Systems Consolidation. However, whether they are necessary for memory retrieval as well remains unclear. We, therefore, used c-Fos immunohistochemistry and reversible inactivations to investigate the role of the ATN and ILN/LT in recent and remote contextual fear memory retrieval in rats. The results confirm a differential role of the ATN and ILN/LT in Systems Consolidation, showing the involvement of the ATN in recent but not remote memory retrieval. This study also pinpoints which specific nuclei are involved in retrieval: the anterodorsal nucleus for recent memories, and the lateral mediodorsal nucleus for remote memories. Lastly, we also show that the ATN are not involved in reConsolidation. Together, the results suggest that these nuclei provide critical feedback for successful memory retrieval and Systems Consolidation.
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Differential role of the anterior and intralaminar/lateral thalamic nuclei in Systems Consolidation and reConsolidation.
Brain structure & function, 2017Co-Authors: Joëlle Lopez, Karine Gamache, Carmelo Milo, Karim NaderAbstract:The anterior thalamic nuclei (ATN) and the intralaminar/lateral thalamic nuclei (ILN/LT) play different roles in memory processes. The ATN are believed to be part of an extended hippocampal system, and the ILN/LT have strong connections with the medial prefrontal cortex. It was shown that the ILN/LT are involved in Systems Consolidation. However, whether they are necessary for memory retrieval as well remains unclear. We, therefore, used c-Fos immunohistochemistry and reversible inactivations to investigate the role of the ATN and ILN/LT in recent and remote contextual fear memory retrieval in rats. The results confirm a differential role of the ATN and ILN/LT in Systems Consolidation, showing the involvement of the ATN in recent but not remote memory retrieval. This study also pinpoints which specific nuclei are involved in retrieval: the anterodorsal nucleus for recent memories, and the lateral mediodorsal nucleus for remote memories. Lastly, we also show that the ATN are not involved in reConsolidation. Together, the results suggest that these nuclei provide critical feedback for successful memory retrieval and Systems Consolidation.
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Context-dependent modulation of hippocampal and cortical recruitment during remote spatial memory retrieval.
Hippocampus, 2011Co-Authors: Joëlle Lopez, Brigitte Cosquer, Jean-christophe Cassel, Karine Herbeaux, Michel Engeln, Christophe Muller, Christine Lazarus, Christian Kelche, Bruno Bontempi, Anne P. De VasconcelosAbstract:According to Systems Consolidation, as hippocampal-dependent memories mature over time, they become additionally (or exclusively) dependent on extra-hippocampal structures. We assessed the recruitment of hippocampal and cortical structures on remote memory retrieval in a performance-degradation resistant (PDR; no performance degradation with time) versus performance-degradation prone (PDP; performance degraded with time) context. Using a water-maze task in two contexts with a hidden platform and three control conditions (home cage, visible platform with or without access to distal cues), we compared neuronal activation (c-Fos imaging) patterns in the dorsal hippocampus and the medial prefrontal cortex (mPFC) after the retrieval of recent (5 days) versus remote (25 days) spatial memory. In the PDR context, the hippocampus exhibited greater c-Fos protein expression on remote than recent memory retrieval, be it in the visible or hidden platform group. In the PDP context, hippocampal activation increased at the remote time point and only in the hidden platform group. In the anterior cingulate cortex, c-Fos expression was greater for remote than for recent memory retrieval and only in the PDR context. The necessity of the mPFC for remote memory retrieval in the PDR context was confirmed using region-specific lidocaine inactivation, which had no impact on recent memory. Conversely, inactivation of the dorsal hippocampus impaired both recent and remote memory in the PDR context, and only recent memory in the PDP context, in which remote memory performance was degraded. While confirming that neuronal circuits supporting spatial memory Consolidation are reorganized in a time-dependent manner, our findings further indicate that mPFC and hippocampus recruitment (i) depends on the content and perhaps the strength of the memory and (ii) may be influenced by the environmental conditions (e.g., cue saliency, complexity) in which memories are initially formed and subsequently recalled.
Rodrigo O. Sierra - One of the best experts on this subject based on the ideXlab platform.
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Chronic fluoxetine prevents fear memory generalization and enhances subsequent extinction by remodeling hippocampal dendritic spines and slowing down Systems Consolidation.
Translational psychiatry, 2019Co-Authors: Lizeth K. Pedraza, Rodrigo O. Sierra, Fernanda N. Lotz, Marcelo Giachero, Walquiria Nunes-souza, Lucas De Oliveira AlvaresAbstract:Fear memory overgeneralization contributes to the genesis and persistence of anxiety disorders and is a central hallmark in the pathophysiology of post-traumatic stress disorder (PTSD). Recent findings suggest that fear generalization is closely related to hippocampal dependency during retrieval. The selective serotonin reuptake inhibitor (SSRI) fluoxetine has been used as a first-line treatment for PTSD; however, how it exerts its therapeutic effect remains a matter of debate. Here, using contextual fear conditioning in rats, we show that chronic fluoxetine treatment prevents fear generalization and enhances subsequent extinction. Moreover, fluoxetine treatment after extinction prevents spontaneous recovery. The mechanism through which fluoxetine affects generalization and extinction seems to be through the postponement of Systems Consolidation, thereby maintaining hippocampal involvement during retrieval. Such an effect relies on a remodeling of dendritic spines in the hippocampus, as well as the number of mature, mushroom-type spines promoted by fluoxetine treatment. In order to further investigate whether fear generalization is a potential predictor of extinction effectiveness, we categorized a large naive population according to their generalization rate. We found that discriminator rats showed a better extinction profile compared to generalizers, suggesting that the generalization rate predicts extinction effectiveness. Hence, we propose that the therapeutic strategy of choice should take into account the extension of memory generalization, in which therapies based on extinction could induce a better outcome in patients who present less fear overgeneralization. These results open new avenues for the development of interventions that prevent fear generalization by maintaining memory dependency of the hippocampus.
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ReConsolidation-induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens.
Hippocampus, 2017Co-Authors: Rodrigo O. Sierra, Lizeth K. Pedraza, Ana Paula Crestani, Lucas De Oliveira Alvares, Josué Haubrich, Fabiana Santana, Flávia Z. Boos, Querusche Klippel Zanona, Maria Elisa Calcagnotto, Jorge Alberto QuillfeldtAbstract:Systems Consolidation is a time-dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization-dependent mechanism interpreted as reConsolidation, that restored the normal course of Systems Consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation-induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1-anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying Systems Consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reConsolidation-driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of Systems Consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.
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Sequential learning during contextual fear conditioning guides the rate of Systems Consolidation: Implications for Consolidation of multiple memory traces.
Hippocampus, 2017Co-Authors: Lizeth K. Pedraza, Jorge Alberto Quillfeldt, Rodrigo O. Sierra, Ana Paula Crestani, Lucas De Oliveira AlvaresAbstract:Systems Consolidation has been described as a time-dependent reorganization process involving the neocortical and hippocampal networks underlying memory storage and retrieval. Previous studies of our lab were able to demonstrate that Systems Consolidation is a dynamic process, rather than a merely passive, time-dependent phenomenon. Here, we studied the influence of sequential learning in contextual fear conditioning (CFC) with different training intensities in the time-course of hippocampal dependency and contextual specificity. We found that sequential learning with high-intensity shocks during CFC induces generalization of the first learning (context A) and maintains contextual specificity of the second learning (context B) 15 days after acquisition. Moreover, subsequent experiences reorganize brain structures involved in retrieval, accelerating the involvement of cortical structures and diminishing the hippocampal participation. Exposure to original context before novelty seems to only induce context specificity in hippocampal-dependent memories. We propose that Systems Consolidation could be considered a potential biological mechanism for reducing possible interferences between similar memory traces. © 2017 Wiley Periodicals, Inc.
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The dynamic nature of Systems Consolidation: Stress during learning as a switch guiding the rate of the hippocampal dependency and memory quality
Hippocampus, 2015Co-Authors: Lizeth K. Pedraza, Jorge Alberto Quillfeldt, Rodrigo O. Sierra, Josué Haubrich, Flávia Z. Boos, Lucas De Oliveira AlvaresAbstract:Memory fades over time, becoming more schematic or abstract. The loss of contextual detail in memory may reflect a time-dependent change in the brain structures supporting memory. It has been well established that contextual fear memory relies on the hippocampus for expression shortly after learning, but it becomes hippocampus-independent at a later time point, a process called Systems Consolidation. This time-dependent process correlates with the loss of memory precision. Here, we investigated whether training intensity predicts the gradual decay of hippocampal dependency to retrieve memory, and the quality of the contextual memory representation over time. We have found that training intensity modulates the progressive decay of hippocampal dependency and memory precision. Strong training intensity accelerates Systems Consolidation and memory generalization in a remarkable timeframe match. The mechanisms underpinning such process are triggered by glucocorticoid and noradrenaline released during training. These results suggest that the stress levels during emotional learning act as a switch, determining the fate of memory quality. Moderate stress will create a detailed memory, whereas a highly stressful training will develop a generic gist-like memory.
