scholarly journals PICK1 regulates AMPA receptor endocytosis via direct interactions with AP2 α-appendage and dynamin

2017 ◽  
Vol 216 (10) ◽  
pp. 3323-3338 ◽  
Author(s):  
Maria Fiuza ◽  
Christine M. Rostosky ◽  
Gabrielle T. Parkinson ◽  
Alexei M. Bygrave ◽  
Nagaraj Halemani ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Molecular Mechanisms ◽  
Diverse Range ◽  
Bar Domain ◽  
Receptor Endocytosis ◽  
The Core ◽  
Cargo Proteins ◽  
Nmdar Activation ◽  
Activity Dependent

Clathrin-mediated endocytosis (CME) is used to internalize a diverse range of cargo proteins from the cell surface, often in response to specific signals. In neurons, the rapid endocytosis of GluA2-containing AMPA receptors (AMPARs) in response to NMDA receptor (NMDAR) stimulation causes a reduction in synaptic strength and is the central mechanism for long-term depression, which underlies certain forms of learning. The mechanisms that link NMDAR activation to CME of AMPARs remain elusive. PICK1 is a BAR domain protein required for NMDAR-dependent reductions in surface GluA2; however, the molecular mechanisms involved are unclear. In this study, we show that PICK1 makes direct, NMDAR-dependent interactions with the core endocytic proteins AP2 and dynamin. PICK1–AP2 interactions are required for clustering AMPARs at endocytic zones in dendrites in response to NMDAR stimulation and for consequent AMPAR internalization. We further show that PICK1 stimulates dynamin polymerization. We propose that PICK1 is a cargo-specific endocytic accessory protein required for efficient, activity-dependent AMPAR endocytosis.

scholarly journals GluA2-dependent AMPA receptor endocytosis and the decay of early and late long-term potentiation: possible mechanisms for forgetting of short- and long-term memories

2014 ◽  
Vol 369 (1633) ◽  
pp. 20130141 ◽  
Author(s):  
Oliver Hardt ◽  
Karim Nader ◽  
Yu-Tian Wang
Keyword(s):  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Homeostatic Plasticity ◽  
Molecular Processes ◽  
Short Term ◽  
Receptor Endocytosis ◽  
Term Potentiation ◽  
Short And Long Term ◽  
Activity Dependent

The molecular processes involved in establishing long-term potentiation (LTP) have been characterized well, but the decay of early and late LTP (E-LTP and L-LTP) is poorly understood. We review recent advances in describing the mechanisms involved in maintaining LTP and homeostatic plasticity. We discuss how these phenomena could relate to processes that might underpin the loss of synaptic potentiation over time, and how they might contribute to the forgetting of short-term and long-term memories. We propose that homeostatic downscaling mediates the loss of E-LTP, and that metaplastic parameters determine the decay rate of L-LTP, while both processes require the activity-dependent removal of postsynaptic GluA2-containing AMPA receptors.

scholarly journals Activity-dependent netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus

2018 ◽  
Author(s):  
Stephen D. Glasgow ◽  
Simon Labrecque ◽  
Ian V. Beamish ◽  
Sarah Aufmkolk ◽  
Julien Gibon ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Guidance Cue ◽  
Term Potentiation ◽  
Nmdar Activation ◽  
Genetic Deletion ◽  
Adult Hippocampus ◽  
Activity Dependent

AbstractDynamic trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptors (AMPARs) to synapses is critical for activity-dependent synaptic plasticity underlying learning and memory, however the identity of key molecular effectors remains elusive. Here, we demonstrate that membrane depolarization and N-methyl-D-aspartate receptor (NMDAR) activation triggers secretion of the chemotropic guidance cue netrin-1 from dendrites. Using selective genetic deletion, we show that netrin-1 expression by excitatory neurons is required for NMDAR-dependent long-term potentiation (LTP) in the adult hippocampus. Further, we demonstrate that application of exogenous netrin-1 is sufficient to trigger the potentiation of excitatory glutamatergic transmission at hippocampal Schaffer collateral synapses via Ca2+-dependent recruitment of GluA1-containing AMPARs, promoting the maturation of immature or nascent synapses. These findings identify a central role for activity-dependent release of netrin-1 as a critical effector of synaptic plasticity in the adult hippocampus.

Molecular mechanisms of synaptic consolidation during sleep: BDNF function and dendritic protein synthesis

2005 ◽  
Vol 28 (1) ◽  
pp. 65-66
Author(s):  
Clive R. Bramham
Keyword(s):  
Memory Consolidation ◽  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Dendritic Protein Synthesis ◽  
Mechanisms Of Memory ◽  
Activity Dependent ◽  
Specific Contribution

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.

scholarly journals PDZ protein mediated activity-dependent LTP/LTD developmental switch at rat retinocollicular synapses

2010 ◽  
Vol 298 (6) ◽  
pp. C1572-C1582 ◽  
Author(s):  
Lei Xue ◽  
Fan Zhang ◽  
Xianhua Chen ◽  
Junji Lin ◽  
Jian Shi
Keyword(s):  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Basic Mechanism ◽  
Long Term Effects ◽  
Interacting Protein ◽  
Term Potentiation ◽  
Retinal Input ◽  
Pdz Protein ◽  
Activity Dependent

The insertion of amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors into the plasma membrane and removal via internalization are essential for regulating synaptic strength, which underlies the basic mechanism of learning and memory. The retinocollicular pathway undergoes synaptic refinement during development and shows a wide variety of long-term synaptic changes; however, still little is known about its underlying molecular regulation. Here we report a rapid developmental long-term potentiation (LTP)/long-term depression (LTD) switch and its intracellular mechanism at the rat retinocollicular pathway from postnatal day 5 (P5) to P14. Before P9, neurons always exhibited LTP, whereas LTD was observed only after P10. Blockade of GluR2/3-glutamate receptor-interacting protein (GRIP)/AMPA-receptor-binding protein (ABP)/protein interacting with C kinase 1 (PICK1) interactions with pep2-SVKI could sustain the LTP after P10. This suggests that the LTP/LTD switch relied on PDZ protein activities. Selective interruption of GluR2/3-PICK1 binding by pep2-EVKI blocked the long-lasting effects of both LTP and LTD, suggesting a role for PICK1 in the maintenance of long-term synaptic plasticity. Interestingly, synaptic expression of GRIP increased more than twofold from P7 to P11, whereas ABP and PICK1 expression levels remained stable. Blockade of spontaneous retinal input suppressed this increase and abolished the LTP/LTD switch. These results suggest that the increased GRIP synaptic expression may be a key regulatory factor in mediating the activity-dependent developmental LTP/LTD switch, whereas PICK1 may be required for both LTP and LTD to maintain their long-term effects.

scholarly journals SUSD4 Controls Activity-Dependent Degradation of AMPA Receptor GLUA2 and Synaptic Plasticity

2019 ◽  
Author(s):  
I. González-Calvo ◽  
K. Iyer ◽  
M. Carquin ◽  
A. Khayachi ◽  
F.A. Giuliani ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Motor Coordination ◽  
Transmembrane Protein ◽  
Ubiquitin Ligases ◽  
Potential Contribution ◽  
Dependent Manner ◽  
Activity Dependent

SummaryAt excitatory synapses, the choice between recycling or degradation of glutamate AMPA receptors controls the direction of synaptic plasticity. In this context, how the degradation machinery is targeted to specific synaptic substrates in an activity-dependent manner is not understood. Here we show that SUSD4, a complement-related transmembrane protein, is a tether for HECT ubiquitin ligases of the NEDD4 subfamily, which promote the degradation of a large number of cellular substrates. SUSD4 is expressed by many neuronal populations starting at the time of synapse formation. Loss-of-function of Susd4 in the mouse prevents activity-dependent degradation of the GLUA2 AMPA receptor subunit and long-term depression at cerebellar synapses, and leads to impairment in motor coordination adaptation and learning. SUSD4 could thus act as an adaptor targeting NEDD4 ubiquitin ligases to AMPA receptors during long-term synaptic plasticity. These findings shed light on the potential contribution of SUSD4 mutations to the etiology of neurodevelopmental diseases.

scholarly journals Calcineurin Participation in Hebbian and Homeostatic Plasticity Associated With Extinction

2021 ◽  
Vol 15 ◽  
Author(s):  
Salma E. Reyes-García ◽  
Martha L. Escobar
Keyword(s):  
Molecular Mechanisms ◽  
Long Term Potentiation ◽  
Underlying Mechanism ◽  
Homeostatic Plasticity ◽  
Extinction Process ◽  
Hebbian Plasticity ◽  
Term Potentiation ◽  
Dependent Modification ◽  
Activity Dependent

In nature, animals need to adapt to constant changes in their environment. Learning and memory are cognitive capabilities that allow this to happen. Extinction, the reduction of a certain behavior or learning previously established, refers to a very particular and interesting type of learning that has been the basis of a series of therapies to diminish non-adaptive behaviors. In recent years, the exploration of the cellular and molecular mechanisms underlying this type of learning has received increasing attention. Hebbian plasticity (the activity-dependent modification of the strength or efficacy of synaptic transmission), and homeostatic plasticity (the homeostatic regulation of plasticity) constitute processes intimately associated with memory formation and maintenance. Particularly, long-term depression (LTD) has been proposed as the underlying mechanism of extinction, while the protein phosphatase calcineurin (CaN) has been widely related to both the extinction process and LTD. In this review, we focus on the available evidence that sustains CaN modulation of LTD and its association with extinction. Beyond the classic view, we also examine the interconnection among extinction, Hebbian and homeostatic plasticity, as well as emergent evidence of the participation of kinases and long-term potentiation (LTP) on extinction learning, highlighting the importance of the balance between kinases and phosphatases in the expression of extinction. Finally, we also integrate data that shows the association between extinction and less-studied phenomena, such as synaptic silencing and engram formation that open new perspectives in the field.

scholarly journals AMPA receptor subunit GluR1 (GluA1) serine-845 site is involved in synaptic depression but not in spine shrinkage associated with chemical long-term depression

2011 ◽  
Vol 105 (4) ◽  
pp. 1897-1907 ◽  
Author(s):  
Kaiwen He ◽  
Angela Lee ◽  
Lihua Song ◽  
Patrick O. Kanold ◽  
Hey-Kyoung Lee
Keyword(s):  
Ampa Receptor ◽  
Molecular Mechanisms ◽  
Pyramidal Neurons ◽  
Low Frequency ◽  
Morphological Plasticity ◽  
Mutant Mice ◽  
Long Term Depression ◽  
Spine Head ◽  
Nmdar Activation

The structure of dendritic spines is highly plastic and can be modified by neuronal activity. In addition, there is evidence that spine head size correlates with the synaptic α-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA) receptor (AMPAR) content, which suggests that they may be coregulated. Although there is evidence that there are overlapping mechanisms for structural and functional plasticity, the extent of the overlap needs further investigation. Specifically, it is unknown whether AMPAR levels determine spine size or whether both are regulated via parallel pathways. We studied the correlation between spine structural plasticity and long-term synaptic plasticity following chemical-induced long-term depression (chemLTD). In particular, we examined whether the regulation of AMPARs, which is implicated in LTD, is critical for spine morphological plasticity. We used mutant mice specifically lacking the serine-845 site on the type 1 glutamate receptor (GluR1, or GluA1) subunit of AMPARs (mutants). These mice specifically lack N-methyl-d-aspartate (NMDA) receptor (NMDAR)-dependent LTD and NMDAR activation-induced AMPAR endocytosis. We found that chemLTD causes a rapid and persistent shrinkage in spine head volume of hippocampal CA1 pyramidal neurons in wild types similar to that reported in other studies using low-frequency stimulation (LFS)-induced LTD. Surprisingly, we found that although S845A mutant mice display impaired chemLTD, the shrinkage of spine head volume occurred to a similar magnitude to that observed in wild types. Our results suggest that there is dissociation in the molecular mechanisms underlying functional LTD and spine shrinkage and that GluR1-S845 regulation is not necessary for spine morphological plasticity.

Clustered plasticity in Long-Term Potentiation: How strong synapses persist to maintain long-term memory

Neuroforum ◽  
2018 ◽  
Vol 24 (3) ◽  
pp. A127-A132
Author(s):  
Marina Mikhaylova ◽  
Michael R. Kreutz
Keyword(s):  
Molecular Mechanisms ◽  
Synaptic Weight ◽  
Long Term Potentiation ◽  
Long Term Memory ◽  
Term Memory ◽  
Term Potentiation ◽  
Associated Functions ◽  
Time Periods ◽  
Activity Dependent

Abstract The storage of memory requires at least in part maintenance of long-term potentiation (LTP) in dendritic spine synapses. Neighboring synapses are frequently arranged into functional clusters. At present, it is still unclear how these clusters evolve, why they are stable for longer time periods and how spines interact within a cluster. In this review, we will provide an overview of current concepts of clustered plasticity and we will discuss cellular as well as molecular mechanisms that might be relevant for spine stability and associated functions in the context of LTP. We will propose that dynamics of initially formed clusters depend on compartmentalization of dendrites and that activity-dependent gene expression kicks in to preserve differences in synaptic weight. We will discuss how mechanisms of synaptic tagging, the presence of secretory organelles in dendrites and the incorporation of synaptic scaling factors that are encoded by immediate early genes interact to preserve clustered plasticity.

Russia’s Development Strategy: Guidelines and Restrictions

2008 ◽  
pp. 119-130 ◽  
Author(s):  
V. Senchagov
Keyword(s):  
Economic Development ◽  
Development Strategy ◽  
Conceptual Basis ◽  
The Core ◽  
Economic Development Strategy ◽  
Socio Economic Development ◽  
Rates Of Growth

The core of Russia’s long-term socio-economic development strategy is represented by its conceptual basis. Having considered debating points about the essence and priority of the strategy, the author analyzes the logic and stages of its development as well as possibilities, restrictions and risks of high GDP rates of growth.

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