The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Wickliffe C. Abraham - One of the best experts on this subject based on the ideXlab platform.
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Making Synapses Strong: Metaplasticity Prolongs Associativity of Long-TermMemory by Switching Synaptic Tag Mechanisms
2016Co-Authors: Martin Rothkegel, Wickliffe C. Abraham, Zhi Cheng Xiao, Martin Korte, Sreedharan SajikumarAbstract:One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by a weak event, can capture plasticity-related proteins from a nearby strong input, thus enabling associativity between the 2 (synaptic tagging and capture, STC). So far, STC has been observed for only a limited time of 60 min. Nevertheless, association of weak memory forms can occur beyond this period and its mechanism is not well understood. Here we report that Metaplasticity induced by ryanodine receptor acti-vation or synaptic activation of metabotropic glutamate receptors prolongs the durability of the synaptic tag, thus extending the time window for associative interactions mediating storage of long-term memory. We provide evidence that such Metaplasticity alters the mechanisms of STC from a CaMKII-mediated (in non-primed STC) to a protein kinase Mzeta (PKMζ)-mediated process (in primed STC). Thus the association of weak synapses with strong synapses in the “late ” stage of associative memory formation occurs only through Metaplasticity. The results also reveal that the short-lived, CaMKII-mediated tag may contribute to a mechanism for a fragile form of memory while Metaplasticity enables a PKMζ-mediated synaptic tag capable of prolonged interactions that induce a more stable form of memory that is resistant to reversal
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mechanisms of heterosynaptic Metaplasticity
Philosophical Transactions of the Royal Society B, 2014Co-Authors: Sarah R Hulme, Owen D Jones, Clarke R Raymond, Pankaj Sah, Wickliffe C. AbrahamAbstract:Synaptic plasticity is fundamental to the neural processes underlying learning and memory. Interestingly, synaptic plasticity itself can be dynamically regulated by prior activity, in a process termed 'Metaplasticity', which can be expressed both homosynaptically and heterosynaptically. Here, we focus on heterosynaptic Metaplasticity, particularly long-range interactions between synapses spread across dendritic compartments, and review evidence for intracellular versus intercellular signalling pathways leading to this effect. Of particular interest is our previously reported finding that priming stimulation in stratum oriens of area CA1 in the hippocampal slice heterosynaptically inhibits subsequent long-term potentiation and facilitates long-term depression in stratum radiatum. As we have excluded the most likely intracellular signalling pathways that might mediate this long-range heterosynaptic effect, we consider the hypothesis that intercellular communication may be critically involved. This hypothesis is supported by the finding that extracellular ATP hydrolysis, and activation of adenosine A2 receptors are required to induce the metaplastic state. Moreover, delivery of the priming stimulation in stratum oriens elicited astrocytic calcium responses in stratum radiatum. Both the astrocytic responses and the Metaplasticity were blocked by gap junction inhibitors. Taken together, these findings support a novel intercellular communication system, possibly involving astrocytes, being required for this type of heterosynaptic Metaplasticity.
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stress induced Metaplasticity from synapses to behavior
Neuroscience, 2013Co-Authors: Mathias V Schmidt, Wickliffe C. Abraham, Mouna Maroun, Oliver Stork, Gal RichterlevinAbstract:Synaptic plasticity, specifically long-term potentiation and long-term depression, is thought to be the underlying cellular mechanism for learning and memory processes in the brain. About two decades ago a new concept was introduced, namely Metaplasticity, which comprises changes that modify the properties of synaptic plasticity due to a priming or preconditioning event. While Metaplasticity was initially defined and studied predominantly on a synaptic and cellular level, it soon became apparent that the term could also be very useful to describe plasticity changes on a more global level, including environmental stressors as priming events and altered behavior as outcome measures. We consider here whether it is helpful to conceptualize these latter effects as "behavioral Metaplasticity", and in which sense this view fits into the original concept of Metaplasticity. By integrating the literature on environmental effects on plasticity, especially stress, plus developmental aspects as well as genetic and epigenetic modifications, we shape the framework in which the term "behavioral Metaplasticity" should be considered and discuss research directions that can help to unravel the mechanisms involved in both synaptic and behavioral Metaplasticity.
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emerging roles of Metaplasticity in behaviour and disease
Trends in Neurosciences, 2013Co-Authors: Sarah R Hulme, Owen D Jones, Wickliffe C. AbrahamAbstract:Since its initial conceptualisation, Metaplasticity has come to encompass a wide variety of phenomena and mechanisms, creating the important challenge of understanding how they contribute to network function and behaviour. Here, we present a framework for considering potential roles of Metaplasticity across three domains of function. First, Metaplasticity appears ideally placed to prepare for subsequent learning by either enhancing learning ability generally or by preparing neuronal networks to encode specific content. Second, Metaplasticity can homeostatically regulate synaptic plasticity, and this likely has important behavioural consequences by stabilising synaptic weights while ensuring the ongoing availability of synaptic plasticity. Finally, we discuss emerging evidence that Metaplasticity mechanisms may play a role in disease causally and may serve as a potential therapeutic target.
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Making Synapses Strong: Metaplasticity Prolongs Associativity of Long-Term Memory by Switching Synaptic Tag Mechanisms
Cerebral Cortex, 2012Co-Authors: Martin Rothkegel, Wickliffe C. Abraham, Zhi Cheng Xiao, Martin Korte, Sreedharan SajikumarAbstract:One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by a weak event, can capture plasticity-related proteins from a nearby strong input, thus enabling associativity between the 2 (synaptic tagging and capture, STC). So far, STC has been observed for only a limited time of 60 min. Nevertheless, association of weak memory forms can occur beyond this period and its mechanism is not well understood. Here we report that Metaplasticity induced by ryanodine receptor activation or synaptic activation of metabotropic glutamate receptors prolongs the durability of the synaptic tag, thus extending the time window for associative interactions mediating storage of long-term memory. We provide evidence that such Metaplasticity alters the mechanisms of STC from a CaMKII-mediated (in non-primed STC) to a protein kinase Mzeta (PKMζ)-mediated process (in primed STC). Thus the association of weak synapses with strong synapses in the "late" stage of associative memory formation occurs only through Metaplasticity. The results also reveal that the short-lived, CaMKII-mediated tag may contribute to a mechanism for a fragile form of memory while Metaplasticity enables a PKMζ-mediated synaptic tag capable of prolonged interactions that induce a more stable form of memory that is resistant to reversal.
Peter V. Nguyen - One of the best experts on this subject based on the ideXlab platform.
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induction of β adrenergic Metaplasticity of ltp requires intact anchoring of pka
Learning & Memory, 2019Co-Authors: Janlyn R Hoffman, Nathan J Brandwein, Peter V. NguyenAbstract:Beta-adrenergic receptors (β-ARs) prime hippocampal synapses to stabilize long-term potentiation (LTP). This "Metaplasticity" can persist for 1-2 h after pharmacologic activation of β-ARs. It requires activation of PKA (cAMP-dependent protein kinase) during β-AR priming. A-kinase anchoring proteins (AKAPs) tether PKA to downstream signaling proteins. We hypothesized that induction of this Metaplasticity requires intact functioning of AKAPs. Acute application of stearated ht31, a membrane-permeant inhibitor of AKAPs, either during β-AR activation 30 min prior to LTP induction or during LTP induction, attenuated the persistence of LTP. A control, inactive ht31 peptide did not affect β-AR-mediated Metaplasticity. These findings implicate PKA anchoring in the induction of β-adrenergic Metaplasticity of LTP.
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norepinephrine triggers Metaplasticity of ltp by increasing translation of specific mrnas
Learning & Memory, 2015Co-Authors: Sabyasachi Maity, Sean Rah, Nahum Sonenberg, Christos G Gkogkas, Peter V. NguyenAbstract:Norepinephrine (NE) is a key modulator of synaptic plasticity in the hippocampus, a brain structure crucially involved in memory formation. NE boosts synaptic plasticity mostly through initiation of signaling cascades downstream from beta (β)-adrenergic receptors (β-ARs). Previous studies demonstrated that a β-adrenergic receptor agonist, isoproterenol, can modify the threshold for long-term potentiation (LTP), a putative cellular mechanism for learning and memory, in a process known as "Metaplasticity." Metaplasticity is the ability of synaptic plasticity to be modified by prior experience. We asked whether NE itself could engage metaplastic mechanisms in area CA1 of mouse hippocampal slices. Using extracellular field potential recording and stimulation, we show that application of NE (10 µM), which did not alter basal synaptic strength, enhances the future maintenance of LTP elicited by subthreshold, high-frequency stimulation (HFS: 1 × 100 Hz, 1 sec). HFS applied 30 min after NE washout induced long-lasting (>4 h) LTP, which was significantly extended in duration relative to HFS alone. This NE-induced Metaplasticity required β1-AR activation, as coapplication of the β1-receptor antagonist CGP-20712A (1 µM) attenuated maintenance of LTP. We also found that NE-mediated Metaplasticity was translation- and transcription-dependent. Polysomal profiles of CA1 revealed increased translation rates for specific mRNAs during NE-induced Metaplasticity. Thus, activation of β-ARs by NE primes synapses for future long-lasting plasticity on time scales extending beyond fast synaptic transmission; this may facilitate neural information processing and the subsequent formation of lasting memories.
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Prescient Synapses: Gating Future Neuronal Consciousness Through Synaptic Tagging and Metaplasticity
Synaptic Tagging and Capture, 2014Co-Authors: Steven A. Connor, Peter V. NguyenAbstract:Restriction of synaptic plasticity to time frames dictated by fast synaptic transmission would yield neuronal networks incapable of encoding qualitatively rich memories. The ability to associate and encode temporally disparate aspects of a memory confers significant survival advantages. The temporal spread of everyday experiences necessitates broad time windows for synaptic encoding of multiple related events. By extending the time frame in which events can be associated at a synaptic level, and biasing synapses towards a plasticity-conducive state, synaptic tagging and Metaplasticity provide potent mechanisms for enhancing memory quality in the brain. Tagging and Metaplasticity serve as gateways for augmenting neuronal consciousness. Priming of future synaptic plasticity can enhance neuronal detection, encoding, and association of salient future events, and it can facilitate storage of detailed memories. We review key intracellular signalling mechanisms that initiate lasting changes in the ability of synapses to undergo Metaplasticity, along with leading candidate synaptic tags that facilitate Metaplasticity. We also speculate on how these phenomena bolster neuronal consciousness to sculpt the brain’s capacity to dynamically encode and store information.
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Homosynaptic and Heterosynaptic Inhibition of Synaptic Tagging and Capture of Long-Term Potentiation by Previous Synaptic Activity
Journal of Neuroscience, 2005Co-Authors: Jennie Z. Young, Peter V. NguyenAbstract:Long-term potentiation (LTP) is an enhancement of synaptic strength that may contribute to information storage in the mammalian brain. LTP expression can be regulated by previous synaptic activity, a process known as "Metaplasticity." Cell-wide occurrence of Metaplasticity may regulate synaptic strength. However, few reports have demonstrated Metaplasticity at synapses that are silent during activity at converging synaptic inputs. We describe a novel form of cell-wide Metaplasticity in hippocampal area CA1. Low-frequency stimulation (LFS) decreased the stability of long-lasting LTP ["late" LTP (L-LTP)] induced later at the same inputs (homosynaptic inhibition) and at other inputs converging on the same postsynaptic cells (heterosynaptic inhibition). Significantly, heterosynaptic inhibition of L-LTP also occurred across basal and apical dendrites ("heterodendritic" inhibition). Because transient early LTP (E-LTP) was not affected by previous LFS, we examined the effects of LFS on the consolidation of E-LTP to L-LTP. The duration of E-LTP induced at one set of inputs can be extended by capturing L-LTP-associated gene products generated by previous activity at other inputs to the same postsynaptic neurons. LFS applied homosynaptically or heterosynaptically before L-LTP induction did not impair synaptic capture by subsequent E-LTP stimulation, suggesting that LFS does not impair L-LTP-associated transcription. In contrast, LFS applied just before E-LTP (homosynaptically or heterosynaptically) prevented synaptic tagging, and capture of L-LTP expression. Thus, LFS inhibits synaptic tagging to impair expression of subsequent L-LTP. Such anterograde inhibition represents a novel way in which synaptic activity can regulate the expression of future long-lasting synaptic plasticity in a cell-wide manner.
Sreedharan Sajikumar - One of the best experts on this subject based on the ideXlab platform.
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Making Synapses Strong: Metaplasticity Prolongs Associativity of Long-TermMemory by Switching Synaptic Tag Mechanisms
2016Co-Authors: Martin Rothkegel, Wickliffe C. Abraham, Zhi Cheng Xiao, Martin Korte, Sreedharan SajikumarAbstract:One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by a weak event, can capture plasticity-related proteins from a nearby strong input, thus enabling associativity between the 2 (synaptic tagging and capture, STC). So far, STC has been observed for only a limited time of 60 min. Nevertheless, association of weak memory forms can occur beyond this period and its mechanism is not well understood. Here we report that Metaplasticity induced by ryanodine receptor acti-vation or synaptic activation of metabotropic glutamate receptors prolongs the durability of the synaptic tag, thus extending the time window for associative interactions mediating storage of long-term memory. We provide evidence that such Metaplasticity alters the mechanisms of STC from a CaMKII-mediated (in non-primed STC) to a protein kinase Mzeta (PKMζ)-mediated process (in primed STC). Thus the association of weak synapses with strong synapses in the “late ” stage of associative memory formation occurs only through Metaplasticity. The results also reveal that the short-lived, CaMKII-mediated tag may contribute to a mechanism for a fragile form of memory while Metaplasticity enables a PKMζ-mediated synaptic tag capable of prolonged interactions that induce a more stable form of memory that is resistant to reversal
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Metaplasticity of synaptic tagging and capture memory beyond the circle
2015Co-Authors: Mahima Sharma, Sreedharan SajikumarAbstract:The Synaptic Tagging and Capture (STC) process, characterized by the tag-plasticity related protein (PRP) interactions, forms the basis of associative memories. The STC hypothesis provides a conceptual basis of how short-term forms of plasticity are transformed into long-term forms of plasticity in an associative and time-dependent manner. The capacity of a synapse to undergo plastic changes in the future is prone to modification by the previous neural activity—a phenomenon referred to as Metaplasticity. The two critical components of the STC process—threshold and time-window—can be modified by a metaplastic stimulus. Metaplasticity of STC has important implications in learning and memory. It lowers the threshold for memory storage and prolongs the associativity for long-term memory. Furthermore, Metaplasticity can effectively prevent synaptic competition in recently potentiated synaptic compartments. Taking these outcomes into consideration, it is clear that aberrant Metaplasticity might be the basis for cognitive dysfunction. Amelioration of the cognitive dysfunction in a number of neurodegenerative diseases entails full understanding of the contributions of Metaplasticity mechanisms to cognitive dysfunction. In this chapter we will review the Metaplasticity of STC along with its implications in learning and memory.
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Making Synapses Strong: Metaplasticity Prolongs Associativity of Long-Term Memory by Switching Synaptic Tag Mechanisms
Cerebral Cortex, 2012Co-Authors: Martin Rothkegel, Wickliffe C. Abraham, Zhi Cheng Xiao, Martin Korte, Sreedharan SajikumarAbstract:One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by a weak event, can capture plasticity-related proteins from a nearby strong input, thus enabling associativity between the 2 (synaptic tagging and capture, STC). So far, STC has been observed for only a limited time of 60 min. Nevertheless, association of weak memory forms can occur beyond this period and its mechanism is not well understood. Here we report that Metaplasticity induced by ryanodine receptor activation or synaptic activation of metabotropic glutamate receptors prolongs the durability of the synaptic tag, thus extending the time window for associative interactions mediating storage of long-term memory. We provide evidence that such Metaplasticity alters the mechanisms of STC from a CaMKII-mediated (in non-primed STC) to a protein kinase Mzeta (PKMζ)-mediated process (in primed STC). Thus the association of weak synapses with strong synapses in the "late" stage of associative memory formation occurs only through Metaplasticity. The results also reveal that the short-lived, CaMKII-mediated tag may contribute to a mechanism for a fragile form of memory while Metaplasticity enables a PKMζ-mediated synaptic tag capable of prolonged interactions that induce a more stable form of memory that is resistant to reversal.
Mark F. Bear - One of the best experts on this subject based on the ideXlab platform.
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obligatory role of nr2a for Metaplasticity in visual cortex
Neuron, 2007Co-Authors: Benjamin D Philpot, Kathleen K A Cho, Mark F. BearAbstract:SUMMARY Light deprivation lowers the threshold for longterm depression (LTD) and long-term potentiation (LTP) in visual cortex by a process termed Metaplasticity, but the mechanism is unknown. The decreased LTD/P threshold correlates with a decrease in the ratio of NR2A to NR2B subunits of cortical NMDA receptors (NMDARs) and a slowing of NMDAR-mediated excitatory postsynaptic currents (EPSCs). However, whether and how changes in NR2 subunit expression contribute to LTD and LTP have been controversial. In the present study, we used an NR2A knockout (KO) mouse to examine the roleofthis subunitintheexperience-dependent modulation of NMDAR properties, LTD, and LTP. We found that deletion of NR2A abrogates the effects of visual experience on NMDAR EPSCs and prevents Metaplasticity of LTP and LTD. These data support the hypothesis that experience-dependent changes in NR2A/B are functionally significant and yield a mechanism for an adjustable synaptic modification threshold in visual cortex.
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Metaplasticity: the plasticity of synaptic plasticity
Trends in Neurosciences, 1996Co-Authors: Wickliffe C. Abraham, Mark F. BearAbstract:Abstract In thi paper, we review experimental evidence for a novel form of persistent synaptic plasticity we call Metaplasticity. Metaplasticity is induced by synaptic or cellular activity, but it is not necessarilly expressed as a change in the efficacy of normal synaptic transmission. Instead, it is manifest as a change in the ability to induce subsequent synaptic plasticity such as long-term potentiation or depression, Thus Metaplasticity is higher-order form of synaptic plasticity. Metaplasticity might involve alterations in NMDA-receptor function in some cases, but there are many other candidate mechanisms. The induction of Metaplasticity complicates the interpretation of many commonly studied aspects of synaptic plasticity, such as saturation and biochemical correlates.
Martin Rothkegel - One of the best experts on this subject based on the ideXlab platform.
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Making Synapses Strong: Metaplasticity Prolongs Associativity of Long-TermMemory by Switching Synaptic Tag Mechanisms
2016Co-Authors: Martin Rothkegel, Wickliffe C. Abraham, Zhi Cheng Xiao, Martin Korte, Sreedharan SajikumarAbstract:One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by a weak event, can capture plasticity-related proteins from a nearby strong input, thus enabling associativity between the 2 (synaptic tagging and capture, STC). So far, STC has been observed for only a limited time of 60 min. Nevertheless, association of weak memory forms can occur beyond this period and its mechanism is not well understood. Here we report that Metaplasticity induced by ryanodine receptor acti-vation or synaptic activation of metabotropic glutamate receptors prolongs the durability of the synaptic tag, thus extending the time window for associative interactions mediating storage of long-term memory. We provide evidence that such Metaplasticity alters the mechanisms of STC from a CaMKII-mediated (in non-primed STC) to a protein kinase Mzeta (PKMζ)-mediated process (in primed STC). Thus the association of weak synapses with strong synapses in the “late ” stage of associative memory formation occurs only through Metaplasticity. The results also reveal that the short-lived, CaMKII-mediated tag may contribute to a mechanism for a fragile form of memory while Metaplasticity enables a PKMζ-mediated synaptic tag capable of prolonged interactions that induce a more stable form of memory that is resistant to reversal
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Making Synapses Strong: Metaplasticity Prolongs Associativity of Long-Term Memory by Switching Synaptic Tag Mechanisms
Cerebral Cortex, 2012Co-Authors: Martin Rothkegel, Wickliffe C. Abraham, Zhi Cheng Xiao, Martin Korte, Sreedharan SajikumarAbstract:One conceptual mechanism for the induction of associative long-term memory is that a synaptic tag, set by a weak event, can capture plasticity-related proteins from a nearby strong input, thus enabling associativity between the 2 (synaptic tagging and capture, STC). So far, STC has been observed for only a limited time of 60 min. Nevertheless, association of weak memory forms can occur beyond this period and its mechanism is not well understood. Here we report that Metaplasticity induced by ryanodine receptor activation or synaptic activation of metabotropic glutamate receptors prolongs the durability of the synaptic tag, thus extending the time window for associative interactions mediating storage of long-term memory. We provide evidence that such Metaplasticity alters the mechanisms of STC from a CaMKII-mediated (in non-primed STC) to a protein kinase Mzeta (PKMζ)-mediated process (in primed STC). Thus the association of weak synapses with strong synapses in the "late" stage of associative memory formation occurs only through Metaplasticity. The results also reveal that the short-lived, CaMKII-mediated tag may contribute to a mechanism for a fragile form of memory while Metaplasticity enables a PKMζ-mediated synaptic tag capable of prolonged interactions that induce a more stable form of memory that is resistant to reversal.