Qual Journals: Difference between revisions
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==Rao-Ruiz • Spijker • 2011 • Nature Neuroscience== | ==Rao-Ruiz • Spijker • 2011 • Nature Neuroscience== | ||
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*GluR3 50% 50% 100% | *GluR3 50% 50% 100% | ||
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[[AMPAR]] trafficking to and from the synapse has been one of the most fascinating and intriguing areas of neuroscience over the past 20 years, as it underlies [[LTP]] and LTD—processes that underlie at least some aspects of memory and learning. Much progress has been made in identifying the proteins involved in [[AMPAR]] insertion into and removal from the synapse; many of the molecular mechanisms contributing to these events are also clear. However, it is still not clear how the receptors diffuse laterally to and from the synapses, nor is it clear how they are directed to and from the complex of proteins present in the PSD. We also have to remember that most of the information contributing to this progress has come from cultured neocortical neurons from rodents, genetically or otherwise manipulated to KO or overexpress proteins of interest. That such studies cannot provide all the answers are illustrated by the wealth of conflicting results that have been obtained, and most graphically by the recent paper of Granger et al. which, at first sight, seems to have overturned a consensus on the role of [[AMPAR]] subunits and their C-terminal tails in [[LTP]] that took a wealth of data and 10 years to establish. It would seem that the way forward is to develop new in vivo methods to resolve these contradictions and stimulate further progress in this exciting area of neuroscience. | [[AMPAR]] trafficking to and from the synapse has been one of the most fascinating and intriguing areas of neuroscience over the past 20 years, as it underlies [[LTP]] and LTD—processes that underlie at least some aspects of memory and learning. Much progress has been made in identifying the proteins involved in [[AMPAR]] insertion into and removal from the synapse; many of the molecular mechanisms contributing to these events are also clear. However, it is still not clear how the receptors diffuse laterally to and from the synapses, nor is it clear how they are directed to and from the complex of proteins present in the PSD. We also have to remember that most of the information contributing to this progress has come from cultured neocortical neurons from rodents, genetically or otherwise manipulated to KO or overexpress proteins of interest. That such studies cannot provide all the answers are illustrated by the wealth of conflicting results that have been obtained, and most graphically by the recent paper of Granger et al. which, at first sight, seems to have overturned a consensus on the role of [[AMPAR]] subunits and their C-terminal tails in [[LTP]] that took a wealth of data and 10 years to establish. It would seem that the way forward is to develop new in vivo methods to resolve these contradictions and stimulate further progress in this exciting area of neuroscience. | ||
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==Hayashi · Shi · Esteban · Piccini · Poncer · Malinow • 2000 • Science== | ==Hayashi · Shi · Esteban · Piccini · Poncer · Malinow • 2000 • Science== | ||
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==Bats • Groc • Choquet • 2007 • Cell: Neuron== | |||
{{SlideBox|The Interaction between Stargazin and PSD-95 Regulates AMPA Receptor Surface Trafficking| | |||
===Abstract=== | |||
Accumulation of AMPA receptors at synapses is a fundamental feature of glutamatergic synaptic transmission. Stargazin, a member of the TARP family, is an AMPAR auxiliary subunit allowing interaction of the receptor with scaffold proteins of the postsynaptic density, such as PSD-95. How PSD-95 and Stargazin regulate AMPAR number in synaptic membranes remains elusive. We show, using single quantum dot and FRAP imaging in live hippocampal neurons, that exchange of AMPAR by lateral diffusion between extrasynaptic and synaptic sites mostly depends on the interaction of Stargazin with PSD-95 and not upon the GluR2 AMPAR subunit C terminus. Disruption of interactions between Stargazin and PSD-95 strongly increases AMPAR surface diffusion, preventing AMPAR accumulation at postsynaptic sites. Furthermore, AMPARs and Stargazin diffuse as complexes in and out synapses. These results propose a model in which the Stargazin- PSD-95 interaction plays a key role to trap and transiently stabilize diffusing AMPARs in the postsynaptic density. | |||
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[[Category:Qual]] | [[Category:Qual]] | ||
Revision as of 16:49, 27 May 2013
| Qual | Qual Journals | Quantum Dots | AMPA Receptor | SAP |
Tardin • Cognet • Bats • Lounis • Choquet • 2003 • The EMBO Journal
Direct imaging of lateral movements of AMPA receptors inside synapses
- Statements
Trafficking of AMPAR in and out of synapses is crucial for synaptic plasticity. Protocols that induce plasticity of synaptic transmission in culture result in changes of AMPAR concentration at synapses and are thought to mimic at the molecular level the processes of LTP and LTD.
Membrane trafficking may occur outside of the synapse and accumulate at the PSD after a short delay (Passafaro et al. 2001). Altogether, a unified picture of the postsynaptic density could be one where receptors are immobilized for transient periods of time related to the receptor-scaffold affinity. This could also be true of NMDA receptors (Tovar and Westbrook, 2002).
- Findings
Application of glutamate increased the diffusion rate of GluR2-containting AMPAR whereas a protocol designed to induce calcium influx (stimulation of NMDAR with glycine, glutamate) reduced the percentage of diffusible AMPARs at the PSD. Bath application of 100 uM glutamate caused an 85% increase in AMPAR endocytosis within 15 min (corresponding to a 22% drop in total membrane expression). Conversely , the calcium influx protocol (20 uM biccuculine, 1 uM strychnine, 200 uM glycine) caused a 59% increase in AMPAR membrane expression. Glutamate caused a 55% increase in AMPAR diffusion within synapses, but did not change diffusion outside synapses. Furthermore, glutamate decreased the number of completely immobile AMPARs by 30%. Interestingly, Glutamate causes endocytosis of AMPARs, and internal AMPARs are immobile. Therefore it seems like glutamate may be causing a general endocytotic episode at non-synaptic AMPARs, perhaps not even at the synapse that received the glutamate application. In a parallel effect, it was found that blocking calcium with BAPTA increased the % of mobile AMPARs. Newly inserted receptors were found to be initially diffusive and then stabilized at synaptic sites. In summary, they found that bath application of glutamate induces rapid depletion of AMPARs from PSDs increases synaptic diffusion rate, decreases % of completely immobile receptors, increases proportion of receptors in the area surrounding the synapse (juxtasynaptic region). Activation of NMDARs results in increased surface expression of AMPARs -- in the first few minutes there is mainly a decrease in the proportion of immobile synaptic receptors, but after 40 min, both diffusion rates and percentages of immobile synaptic receptors are back to control values and the proportion of juxtasynaptic receptors is decreased. This observation relates to the fate of newly exocytosed AMPARs: using cleavable extracellular tags, it was observed that at early times after exocytosis, new GluR1 containing AMPARs are diffusively distributed along dendrites. This is followed by their lateral translocation and accumulation into synapses (Passafaro et al., 2001). GluR2 subunits were addressed directly at synapses. In our experiments, we followed the movement of native GluR2 containing AMPARs, where the data suggests that at the level of synapses themselves, newly added receptors are initially diffusive and then stabilize over time.
AMPA receptors that lack edited GluA2 subunits have high single channel conductance, are permeable to Ca2+, are blocked by polyamines causing inward rectification at depolarized potentials.
- 100 uM glutamate - within 15 min
- 85% increase in AMPAR endocytosis
- 22% drop in total membrane expression
- 55% increase in AMPAR diffusion rate within synapses
- 0% increase in AMPAR diffusion rate outside synapses
- 30% decrease in completely immobile AMPAR at PSD
--
- Start: 100 AMPARs in PSD
- Usual endocytosis rate: -0.25% / min
- Add: 100 uM glutamate
- New endocytosis rate: -1.5% / min
- Time: 15 min
- Final: 77.5 AMPARs
- calcium influx protocol (20 uM biccuculine, 1 uM strychnine, 200 uM glycine)
- 59% increase in AMPAR expression
--
- Start: 100 AMPARs in PSD
- Usual endocytosis rate: -0.25% / min
- Add: NMDA antagonists above
- New exocytosis rate: +4% / min
- Time: 15 min
- Final: 160 AMPARs