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Jorge Alberto Quillfeldt - One of the best experts on this subject based on the ideXlab platform.
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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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Synaptic Consolidation as a temporally variable process: Uncovering the parameters modulating its time-course.
Neurobiology of learning and memory, 2018Co-Authors: Mirelle Araujo Casagrande, Josué Haubrich, Lizeth K. Pedraza, Bruno Popik, Jorge Alberto Quillfeldt, Lucas De Oliveira AlvaresAbstract:Abstract Memories are not instantly created in the brain, requiring a gradual stabilization process called Consolidation to be stored and persist in a long-lasting manner. However, little is known whether this time-dependent process is dynamic or static, and the factors that might modulate it. Here, we hypothesized that the time-course of Consolidation could be affected by specific learning parameters, changing the time window where memory is susceptible to retroactive interference. In the rodent contextual fear conditioning paradigm, we compared weak and strong training protocols and found that in the latter memory is susceptible to post-training hippocampal inactivation for a shorter period of time. The accelerated Consolidation process triggered by the strong training was mediated by glucocorticoids, since this effect was blocked by pre-training administration of metyrapone. In addition, we found that pre-exposure to the training context also accelerates fear memory Consolidation. Hence, our results demonstrate that the time window in which memory is susceptible to post-training interferences varies depending on fear conditioning intensity and contextual familiarity. We propose that the time-course of memory Consolidation is dynamic, being directly affected by attributes of the learning experiences.
Clive R Bramham - One of the best experts on this subject based on the ideXlab platform.
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Control of Synaptic Consolidation in the dentate gyrus: mechanisms, functions, and therapeutic implications.
Progress in brain research, 2007Co-Authors: Clive R BramhamAbstract:Synaptic Consolidation refers to the development and stabilization of protein synthesis-dependent modifications of Synaptic strength as observed during long-term potentiation (LTP) and long-term depression (LTD). Activity-dependent changes in Synaptic strength are thought to underlie memory storage and other adaptive responses of the nervous systems of importance in mood stability, reward behavior, and pain control. This chapter focuses on the mechanisms and functions of Synaptic Consolidation in the dentate gyrus, a critical structure not only in hippocampal memory function, but also in regulation of stress responses and cognitive aspects of depression. Recent evidence suggests that Synaptic Consolidation at excitatory medial perforant path-granule cell synapses requires brain-derived neurotrophic factor (BDNF) signaling and induction of the immediate early gene activity-regulated cytoskeleton-associated protein (Arc). Arc mRNA is strongly induced and transported to dendritic processes following high-frequency stimulation (HFS) that induces LTP in the rat dentate gyrus in vivo. Sustained synthesis of Arc during a surprisingly protracted time-window is required for hyperphosphorylation of actin depolymerizing factor/cofilin and local expansion of the actin cytoskeleton in vivo. Furthermore, this process of Arc-dependent Synaptic Consolidation is activated in response to brief infusion of BDNF. Microarray expression profiling has revealed a panel of BDNF-regulated genes that may cooperate with Arc during Synaptic Consolidation. In addition to regulating gene expression, BDNF signaling modulates the fine localization and biochemical activation of the translation machinery. By modulating the spatial and temporal translation of newly induced (Arc) and constitutively-expressed mRNA in dendrites, BDNF may effectively control the window of Synaptic Consolidation. Dysregulation of BDNF synthesis and Arc function, specifically within the dentate gyrus, is linked to behavioral symptoms and cognitive deficits in animal models of depression and Alzheimer's disease. Therapeutics strategies targeting Synaptic Consolidation hold promise for the future.
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Identification of genes co‐upregulated with Arc during BDNF‐induced long‐term potentiation in adult rat dentate gyrus in vivo
The European journal of neuroscience, 2006Co-Authors: Karin Wibrand, Elhoucine Messaoudi, Bjarte Håvik, Vibeke Steenslid, Roger Løvlie, Vidar M. Steen, Clive R BramhamAbstract:Brain-derived neurotrophic factor (BDNF) is a critical regulator of transcription-dependent adaptive neuronal responses, such as long-term potentiation (LTP). Brief infusion of BDNF into the dentate gyrus of adult anesthetized rats triggers stable LTP at medial perforant path-granule synapses that is transcription-dependent and requires induction of the immediate early gene Arc. Rather than acting alone, Arc is likely to be part of a larger BDNF-induced transcriptional program. Here, we used cDNA microarray expression profiling to search for genes co-upregulated with Arc 3 h after BDNF-LTP induction. Of nine cDNAs encoding for known genes and up-regulated more than four-fold, we selected five genes, Narp, neuritin, ADP-ribosylation factor-like protein-4 (ARL4L), TGF-beta-induced immediate early gene-1 (TIEG1) and CARP, for further validation. Real-time PCR confirmed robust up-regulation of these genes in an independent set of BDNF-LTP experiments, whereas infusion of the control protein cytochrome C had no effect. In situ hybridization histochemistry further revealed up-regulation of all five genes in somata of post-Synaptic granule cells following both BDNF-LTP and high-frequency stimulation-induced LTP. While Arc synthesis is critical for local actin polymerization and stable LTP formation, several of the co-upregulated genes have known functions in excitatory synaptogenesis, axon guidance and glutamate receptor clustering. These results provide novel insight into gene expression responses underlying BDNF-induced Synaptic Consolidation in the adult brain in vivo.
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Brain-derived neurotrophic factor and control of Synaptic Consolidation in the adult brain.
Biochemical Society transactions, 2006Co-Authors: J Soulé, Elhoucine Messaoudi, Clive R BramhamAbstract:Interest in BDNF (brain-derived neurotrophic factor) as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF and its receptor tyrosine kinase TrkB (tropomyosin receptor kinase B) to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and Synaptic plasticity in the adult brain. Development of stable LTP (long-term potentiation) in response to high-frequency stimulation requires new gene expression and protein synthesis, a process referred to as Synaptic Consolidation. Several lines of evidence have implicated endogenous BDNF-TrkB signalling in Synaptic Consolidation. This mini-review emphasizes new insights into the molecular mechanisms underlying this process. The immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is strongly induced and transported to dendritic processes after LTP induction in the dentate gyrus in live rats. Recent work suggests that sustained synthesis of Arc during a surprisingly protracted time-window is required for hyperphosphorylation of actin-depolymerizing factor/cofilin and local expansion of the actin cytoskeleton in vivo. Moreover, this process of Arc-dependent Synaptic Consolidation is activated in response to brief infusion of BDNF. Microarray expression profiling has also revealed a panel of BDNF-regulated genes that may co-operate with Arc during LTP maintenance. In addition to regulating gene expression, BDNF signalling modulates the fine localization and biochemical activation of the translation machinery. By modulating the spatial and temporal translation of newly induced (Arc) and constitutively expressed mRNA in neuronal dendrites, BDNF may effectively control the window of Synaptic Consolidation. These findings have implications for mechanisms of memory storage and mood control.
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Molecular mechanisms of Synaptic Consolidation during sleep: BDNF function and dendritic protein synthesis
Behavioral and Brain Sciences, 2005Co-Authors: Clive R BramhamAbstract:Insights into the role of sleep in the molecular mechanisms of memory Consolidation may come from studies of activity-dependent Synaptic plasticity, such as long-term potentiation (LTP). This commentary posits a specific contribution of sleep to LTP stabilization, in which mRNA transported to dendrites during wakefulness is translated during sleep. Brain-derived neurotrophic factor may drive the translation of newly transported and resident mRNA.
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BDNF function in adult Synaptic plasticity: The Synaptic Consolidation hypothesis
Progress in Neurobiology, 2005Co-Authors: Clive R Bramham, Elhoucine MessaoudiAbstract:Interest in BDNF as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF-TrkB to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and plasticity. Despite individual breakthroughs, an integrated understanding of BDNF function in Synaptic plasticity is lacking. Here, we attempt to distill current knowledge of the molecular mechanisms and function of BDNF in LTP. BDNF activates distinct mechanisms to regulate the induction, early maintenance, and late maintenance phases of LTP. Evidence from genetic and pharmacological approaches is reviewed and tabulated. The specific contribution of BDNF depends on the stimulus pattern used to induce LTP, which impacts the duration and perhaps the subcellular site of BDNF release. Particular attention is given to the role of BDNF as a trigger for protein synthesis-dependent late phase LTP - a process referred to as Synaptic Consolidation. Recent experiments suggest that BDNF activates Synaptic Consolidation through transcription and rapid dendritic trafficking of mRNA encoded by the immediate early gene, Arc. A model is proposed in which BDNF signaling at glutamate synapses drives the translation of newly transported (Arc) and locally stored (i.e., αCaMKII) mRNA in dendrites. In this model BDNF tags synapses for mRNA capture, while Arc translation defines a critical window for Synaptic Consolidation. The biochemical mechanisms by which BDNF regulates local translation are also discussed. Elucidation of these mechanisms should shed light on a range of adaptive brain responses including memory and mood resilience. © 2005 Elsevier Ltd. All rights reserved.
Wulfram Gerstner - One of the best experts on this subject based on the ideXlab platform.
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Optimal Stimulation Protocol in a Bistable Synaptic Consolidation Model.
Frontiers in computational neuroscience, 2019Co-Authors: Chiara Gastaldi, Samuel P. Muscinelli, Wulfram GerstnerAbstract:Synaptic changes induced by neural activity need to be consolidated to maintain memory over a timescale of hours. In experiments, Synaptic Consolidation can be induced by repeating a stimulation protocol several times. However, the effectiveness of Consolidation depends crucially on the repetition frequency of the stimulations. Here we propose a simple mathematical model that allows to systematically study the interaction between the stimulation protocol and Synaptic Consolidation. We show the existence of optimal stimulation protocols in our model which, similarly to LTP experiments, depend on the repetition frequency of the stimulation. Our results show that the complex dependence of LTP on the stimulation frequency emerges naturally from a minimal model with only two bistable variables.
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optimal stimulation protocol in a bistable Synaptic Consolidation model
arXiv: Neurons and Cognition, 2018Co-Authors: Chiara Gastaldi, Samuel P. Muscinelli, Wulfram GerstnerAbstract:Consolidation of Synaptic changes in response to neural activity is thought to be fundamental for memory maintenance over a timescale of hours. In experiments, Synaptic Consolidation can be induced by repeatedly stimulating preSynaptic neurons. However, the effectiveness of such protocols depends crucially on the repetition frequency of the stimulations and the mechanisms that cause this complex dependence are unknown. Here we propose a simple mathematical model that allows us to systematically study the interaction between the stimulation protocol and Synaptic Consolidation. We show the existence of optimal stimulation protocols for our model and, similarly to LTP experiments, the repetition frequency of the stimulation plays a crucial role in achieving Consolidation. Our results show that the complex dependence of LTP on the stimulation frequency emerges naturally from a model which satisfies only minimal bistability requirements.
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A Model of Synaptic ReConsolidation
Frontiers in neuroscience, 2016Co-Authors: David B. Kastner, Lorric Ziegler, Tilo Schwalger, Wulfram GerstnerAbstract:ReConsolidation of memories has mostly been studied at the behavioral and molecular level. Here, we put forward a simple extension of existing computational models of Synaptic Consolidation to capture hippocampal slice experiments that have been interpreted as reConsolidation at the Synaptic level. The model implements reConsolidation through stabilization of consolidated synapses by stabilizing entities combined with an activity-dependent reservoir of stabilizing entities that are immune to protein synthesis inhibition (PSI). We derive a reduced version of our model to explore the conditions under which Synaptic reConsolidation does or does not occur, often referred to as the boundary conditions of reConsolidation. We find that our computational model of Synaptic reConsolidation displays complex boundary conditions. Our results suggest that a limited resource of hypothetical stabilizing molecules or complexes, which may be implemented by protein phosphorylation or different receptor subtypes, can underlie the phenomenon of Synaptic reConsolidation.
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Synaptic Consolidation: from synapses to behavioral modeling.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015Co-Authors: Lorric Ziegler, Friedemann Zenke, David B. Kastner, Wulfram GerstnerAbstract:Synaptic plasticity, a key process for memory formation, manifests itself across different time scales ranging from a few seconds for plasticity induction up to hours or even years for Consolidation and memory retention. We developed a three-layered model of Synaptic Consolidation that accounts for data across a large range of experimental conditions. Consolidation occurs in the model through the interaction of the Synaptic efficacy with a scaffolding variable by a read-write process mediated by a tagging-related variable. Plasticity-inducing stimuli modify the efficacy, but the state of tag and scaffold can only change if a write protection mechanism is overcome. Our model makes a link from depotentiation protocols in vitro to behavioral results regarding the influence of novelty on inhibitory avoidance memory in rats.
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Modeling plasticity across different time scales: the TagTriC model
BMC Neuroscience, 2009Co-Authors: Claudia Clopath, Lorric Ziegler, Eleni Vasilaki, Lars Buesing, Wulfram GerstnerAbstract:Changes in Synaptic efficacies need to be long lasting in order to serve as a substrate for memory. Experimentally, Synaptic plasticity exhibits phases covering: i) the induction of long-term potentiation and depression (LTP/LTD) during the early phase of Synaptic plasticity, ii) the setting of Synaptic tags, a trigger process for protein synthesis, and iii) a slow transition leading to Synaptic Consolidation during the late phase of Synaptic plasticity. We present a mathematical model that describes these different phases of Synaptic plasticity. The model explains a large body of experimental data on Synaptic tagging and capture, cross tagging, and the late phases of LTP and LTD. Moreover, the model accounts for the dependence of LTP and LTD induction upon voltage and preSynaptic stimulation frequency. The stabilization of potentiated synapses during the transition from early to late LTP occurs by protein synthesis dynamics that is shared by groups of synapses. The functional consequence of this shared process is that previously stabilized patterns of strong or weak synapses onto the same postSynaptic neuron are well protected against later changes induced by LTP/LTD protocols at individual synapses. Moreover, the protein synthesis being triggered by a dopamine signal, we establish a link between this neuromodulator and the reward prediction error of reinforcement learning models. See Figure 1. from Eighteenth Annual Computational Neuroscience Meeting: CNS*2009 Berlin, Germany. 18–23 July 2009
Elhoucine Messaoudi - One of the best experts on this subject based on the ideXlab platform.
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Identification of genes co‐upregulated with Arc during BDNF‐induced long‐term potentiation in adult rat dentate gyrus in vivo
The European journal of neuroscience, 2006Co-Authors: Karin Wibrand, Elhoucine Messaoudi, Bjarte Håvik, Vibeke Steenslid, Roger Løvlie, Vidar M. Steen, Clive R BramhamAbstract:Brain-derived neurotrophic factor (BDNF) is a critical regulator of transcription-dependent adaptive neuronal responses, such as long-term potentiation (LTP). Brief infusion of BDNF into the dentate gyrus of adult anesthetized rats triggers stable LTP at medial perforant path-granule synapses that is transcription-dependent and requires induction of the immediate early gene Arc. Rather than acting alone, Arc is likely to be part of a larger BDNF-induced transcriptional program. Here, we used cDNA microarray expression profiling to search for genes co-upregulated with Arc 3 h after BDNF-LTP induction. Of nine cDNAs encoding for known genes and up-regulated more than four-fold, we selected five genes, Narp, neuritin, ADP-ribosylation factor-like protein-4 (ARL4L), TGF-beta-induced immediate early gene-1 (TIEG1) and CARP, for further validation. Real-time PCR confirmed robust up-regulation of these genes in an independent set of BDNF-LTP experiments, whereas infusion of the control protein cytochrome C had no effect. In situ hybridization histochemistry further revealed up-regulation of all five genes in somata of post-Synaptic granule cells following both BDNF-LTP and high-frequency stimulation-induced LTP. While Arc synthesis is critical for local actin polymerization and stable LTP formation, several of the co-upregulated genes have known functions in excitatory synaptogenesis, axon guidance and glutamate receptor clustering. These results provide novel insight into gene expression responses underlying BDNF-induced Synaptic Consolidation in the adult brain in vivo.
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Brain-derived neurotrophic factor and control of Synaptic Consolidation in the adult brain.
Biochemical Society transactions, 2006Co-Authors: J Soulé, Elhoucine Messaoudi, Clive R BramhamAbstract:Interest in BDNF (brain-derived neurotrophic factor) as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF and its receptor tyrosine kinase TrkB (tropomyosin receptor kinase B) to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and Synaptic plasticity in the adult brain. Development of stable LTP (long-term potentiation) in response to high-frequency stimulation requires new gene expression and protein synthesis, a process referred to as Synaptic Consolidation. Several lines of evidence have implicated endogenous BDNF-TrkB signalling in Synaptic Consolidation. This mini-review emphasizes new insights into the molecular mechanisms underlying this process. The immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is strongly induced and transported to dendritic processes after LTP induction in the dentate gyrus in live rats. Recent work suggests that sustained synthesis of Arc during a surprisingly protracted time-window is required for hyperphosphorylation of actin-depolymerizing factor/cofilin and local expansion of the actin cytoskeleton in vivo. Moreover, this process of Arc-dependent Synaptic Consolidation is activated in response to brief infusion of BDNF. Microarray expression profiling has also revealed a panel of BDNF-regulated genes that may co-operate with Arc during LTP maintenance. In addition to regulating gene expression, BDNF signalling modulates the fine localization and biochemical activation of the translation machinery. By modulating the spatial and temporal translation of newly induced (Arc) and constitutively expressed mRNA in neuronal dendrites, BDNF may effectively control the window of Synaptic Consolidation. These findings have implications for mechanisms of memory storage and mood control.
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BDNF function in adult Synaptic plasticity: The Synaptic Consolidation hypothesis
Progress in Neurobiology, 2005Co-Authors: Clive R Bramham, Elhoucine MessaoudiAbstract:Interest in BDNF as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF-TrkB to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and plasticity. Despite individual breakthroughs, an integrated understanding of BDNF function in Synaptic plasticity is lacking. Here, we attempt to distill current knowledge of the molecular mechanisms and function of BDNF in LTP. BDNF activates distinct mechanisms to regulate the induction, early maintenance, and late maintenance phases of LTP. Evidence from genetic and pharmacological approaches is reviewed and tabulated. The specific contribution of BDNF depends on the stimulus pattern used to induce LTP, which impacts the duration and perhaps the subcellular site of BDNF release. Particular attention is given to the role of BDNF as a trigger for protein synthesis-dependent late phase LTP - a process referred to as Synaptic Consolidation. Recent experiments suggest that BDNF activates Synaptic Consolidation through transcription and rapid dendritic trafficking of mRNA encoded by the immediate early gene, Arc. A model is proposed in which BDNF signaling at glutamate synapses drives the translation of newly transported (Arc) and locally stored (i.e., αCaMKII) mRNA in dendrites. In this model BDNF tags synapses for mRNA capture, while Arc translation defines a critical window for Synaptic Consolidation. The biochemical mechanisms by which BDNF regulates local translation are also discussed. Elucidation of these mechanisms should shed light on a range of adaptive brain responses including memory and mood resilience. © 2005 Elsevier Ltd. All rights reserved.
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BDNF function in adult Synaptic plasticity: the Synaptic Consolidation hypothesis.
Progress in neurobiology, 2005Co-Authors: Clive R Bramham, Elhoucine MessaoudiAbstract:Interest in BDNF as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF-TrkB to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and plasticity. Despite individual breakthroughs, an integrated understanding of BDNF function in Synaptic plasticity is lacking. Here, we attempt to distill current knowledge of the molecular mechanisms and function of BDNF in LTP. BDNF activates distinct mechanisms to regulate the induction, early maintenance, and late maintenance phases of LTP. Evidence from genetic and pharmacological approaches is reviewed and tabulated. The specific contribution of BDNF depends on the stimulus pattern used to induce LTP, which impacts the duration and perhaps the subcellular site of BDNF release. Particular attention is given to the role of BDNF as a trigger for protein synthesis-dependent late phase LTP--a process referred to as Synaptic Consolidation. Recent experiments suggest that BDNF activates Synaptic Consolidation through transcription and rapid dendritic trafficking of mRNA encoded by the immediate early gene, Arc. A model is proposed in which BDNF signaling at glutamate synapses drives the translation of newly transported (Arc) and locally stored (i.e., alphaCaMKII) mRNA in dendrites. In this model BDNF tags synapses for mRNA capture, while Arc translation defines a critical window for Synaptic Consolidation. The biochemical mechanisms by which BDNF regulates local translation are also discussed. Elucidation of these mechanisms should shed light on a range of adaptive brain responses including memory and mood resilience.
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BDNF as a Trigger for TransSynaptic Consolidation in the Adult Brain
Synaptic Plasticity and Transsynaptic Signaling, 1Co-Authors: Clive R Bramham, Elhoucine MessaoudiAbstract:The neurotrophin family of signaling proteins, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4i5 are crucially involved in regulating the survival and differentiation of neuronal populations during development (Levi Montalcini, 1987; Davies, 1994; Lewin and Barde, 1996). In addition to these well-established functions in development, a large body of work suggests that neurotrophins continue to shape the structure and function of neuronal connections throughout life (Schnell et al., 1994; Thoenen, 1995; Bonhoeffer, 1996; Prakash et al., 1996; Cabelli et al., 1997; Alsina et al., 2001; Maffei, 2002; Bolanos and Nestler, 2004; Duman, 2004; Tuszynski and Blesch, 2004). While neurotrophins traditionally were thought to operate on a time scale of days and weeks, extremely rapid effects have now been demonstrated on ion channels, neurotransmitter release, axon pathfinding, gene expression and mRNA translation (Song and Poo, 1999; Desai et al., 1999; Schinder and Poo, 2000). It has nevertheless been difficult to pin down precise functions for specific neurotrophins in adulthood. One of the most contested areas is the contribution of neurotrophins to activity-dependent Synaptic plasticity. In a series of recent advances several lines of evidence have converged to specficially implicate BDNF in long-term potentiation (LTP), the most widely studied form of Synaptic plasticity in the adult brain. BDNF is uniquely positioned to regulate Synaptic efficacy through bidirectional effects at the glutamate synapse. The complexity and versatility of BDNF signaling is reflected in the multiple roles of this neurotrophin not only in LTP, but also in modulation of longterm depression (LTD), various forms of short-term Synaptic plasticity, and homeostatic regulation of intrinsic neuronal excitability (Desai et al., 1999; Sermasi et al., 2000; Asztely et al., 2000; Kumura et al., 2000; lkegaya et al., 2002; Jiang et al., 2003). In this chapter we will briefly review key evidence for permissive and instructive actions of BDNF in hippocampal LTP. We will further elaborate on new evidence suggesting that BDNF drives the formation of stable, protein synthesis-dependent LTPa process we refer to as Synaptic Consolidation. A working model for Synaptic Consolidation based on induction of the immediate early gene, ArciArg, and local enhancement of dendritic protein synthesis, is proposed.
Lorric Ziegler - One of the best experts on this subject based on the ideXlab platform.
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A Model of Synaptic ReConsolidation
Frontiers in neuroscience, 2016Co-Authors: David B. Kastner, Lorric Ziegler, Tilo Schwalger, Wulfram GerstnerAbstract:ReConsolidation of memories has mostly been studied at the behavioral and molecular level. Here, we put forward a simple extension of existing computational models of Synaptic Consolidation to capture hippocampal slice experiments that have been interpreted as reConsolidation at the Synaptic level. The model implements reConsolidation through stabilization of consolidated synapses by stabilizing entities combined with an activity-dependent reservoir of stabilizing entities that are immune to protein synthesis inhibition (PSI). We derive a reduced version of our model to explore the conditions under which Synaptic reConsolidation does or does not occur, often referred to as the boundary conditions of reConsolidation. We find that our computational model of Synaptic reConsolidation displays complex boundary conditions. Our results suggest that a limited resource of hypothetical stabilizing molecules or complexes, which may be implemented by protein phosphorylation or different receptor subtypes, can underlie the phenomenon of Synaptic reConsolidation.
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Synaptic Consolidation: from synapses to behavioral modeling.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015Co-Authors: Lorric Ziegler, Friedemann Zenke, David B. Kastner, Wulfram GerstnerAbstract:Synaptic plasticity, a key process for memory formation, manifests itself across different time scales ranging from a few seconds for plasticity induction up to hours or even years for Consolidation and memory retention. We developed a three-layered model of Synaptic Consolidation that accounts for data across a large range of experimental conditions. Consolidation occurs in the model through the interaction of the Synaptic efficacy with a scaffolding variable by a read-write process mediated by a tagging-related variable. Plasticity-inducing stimuli modify the efficacy, but the state of tag and scaffold can only change if a write protection mechanism is overcome. Our model makes a link from depotentiation protocols in vitro to behavioral results regarding the influence of novelty on inhibitory avoidance memory in rats.
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Modeling plasticity across different time scales: the TagTriC model
BMC Neuroscience, 2009Co-Authors: Claudia Clopath, Lorric Ziegler, Eleni Vasilaki, Lars Buesing, Wulfram GerstnerAbstract:Changes in Synaptic efficacies need to be long lasting in order to serve as a substrate for memory. Experimentally, Synaptic plasticity exhibits phases covering: i) the induction of long-term potentiation and depression (LTP/LTD) during the early phase of Synaptic plasticity, ii) the setting of Synaptic tags, a trigger process for protein synthesis, and iii) a slow transition leading to Synaptic Consolidation during the late phase of Synaptic plasticity. We present a mathematical model that describes these different phases of Synaptic plasticity. The model explains a large body of experimental data on Synaptic tagging and capture, cross tagging, and the late phases of LTP and LTD. Moreover, the model accounts for the dependence of LTP and LTD induction upon voltage and preSynaptic stimulation frequency. The stabilization of potentiated synapses during the transition from early to late LTP occurs by protein synthesis dynamics that is shared by groups of synapses. The functional consequence of this shared process is that previously stabilized patterns of strong or weak synapses onto the same postSynaptic neuron are well protected against later changes induced by LTP/LTD protocols at individual synapses. Moreover, the protein synthesis being triggered by a dopamine signal, we establish a link between this neuromodulator and the reward prediction error of reinforcement learning models. See Figure 1. from Eighteenth Annual Computational Neuroscience Meeting: CNS*2009 Berlin, Germany. 18–23 July 2009
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Tag-Trigger-Consolidation: A Model of Early and Late Long-Term-Potentiation and Depression
PLoS Computational Biology, 2008Co-Authors: Claudia Clopath, Lorric Ziegler, Eleni Vasilaki, Lars Büsing, Wulfram GerstnerAbstract:Changes in Synaptic efficacies need to be long-lasting in order to serve as a substrate for memory. Experimentally, Synaptic plasticity exhibits phases covering the induction of long-term potentiation and depression (LTP/LTD) during the early phase of Synaptic plasticity, the setting of Synaptic tags, a trigger process for protein synthesis, and a slow transition leading to Synaptic Consolidation during the late phase of Synaptic plasticity. We present a mathematical model that describes these different phases of Synaptic plasticity. The model explains a large body of experimental data on Synaptic tagging and capture, cross-tagging, and the late phases of LTP and LTD. Moreover, the model accounts for the dependence of LTP and LTD induction on voltage and preSynaptic stimulation frequency. The stabilization of potentiated synapses during the transition from early to late LTP occurs by protein synthesis dynamics that are shared by groups of synapses. The functional consequence of this shared process is that previously stabilized patterns of strong or weak synapses onto the same postSynaptic neuron are well protected against later changes induced by LTP/LTD protocols at individual synapses.
