Synapse-Specific Regulation of AMPA Receptor Subunit Composition by Activity

Harms, Kimberly J.; Tovar, Kenneth R.; Craig, Ann Marie

doi:10.1523/jneurosci.0302-05.2005

Cited by 71 publications

(68 citation statements)

References 56 publications

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“…Interestingly, local synaptic activity reduces the diffusional exchange of GluR1 between synaptic and extrasynaptic domains, resulting in postsynaptic accumulation of GluR1-containing AMPAR. In contrast, at neighbor inactive synapses GluR1 was found to be highly mobile (Ehlers et al, 2007), in agreement with an earlier study showing that synapsespecific silencing of neurotransmission causes a reduction in synaptic GluR1-containing AMPARs, in comparison to nearby active synapses (Harms et al, 2005).…”

Section: Vesicular Traffic Synaptic Targeting and Lateral Membrane Dsupporting

confidence: 91%

Regulation of AMPA receptors and synaptic plasticity

et al. 2009

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Section: Vesicular Traffic Synaptic Targeting and Lateral Membrane Dsupporting

confidence: 91%

Regulation of AMPA receptors and synaptic plasticity

et al. 2009

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“…The finding of evidence for retrograde communication does not exclude the additional possibility of orthograde signaling as a further mechanism of transsynaptic coordination. Orthograde signaling has been invoked to explain how presynaptic activity regulates the gathering together of GluA1 (11,24,49). Full coordination might require a combination of signaling in both directions.…”

Section: Role Of Rapid Ampar-dependent Retrograde Signaling To Presynmentioning

confidence: 99%

“…In principle, coordination could arise from a physical linkage of pre-and postsynaptic elements (discussed in ref. 13) or from a primary up-regulation on one side that drives secondary changes on the other (11,23,24).Additional uncertainty exists regarding the time scale of adaptive changes. At the fly neuromuscular junction (NMJ), adaptation to inactivity depends critically on acute changes in physiological function (25)(26)(27).…”

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Postsynaptic GluA1 enables acute retrograde enhancement of presynaptic function to coordinate adaptation to synaptic inactivity

Lindskog

Groth

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Prolonged blockade of AMPA-type glutamate receptors in hippocampal neuron cultures leads to homeostatic enhancements of preand postsynaptic function that appear correlated at individual synapses, suggesting some form of transsynaptic coordination. The respective modifications are important for overall synaptic strength but their interrelationship, dynamics, and molecular underpinnings are unclear. Here we demonstrate that adaptation begins postsynaptically but is ultimately communicated to presynaptic terminals and expressed as an accelerated turnover of synaptic vesicles. Critical postsynaptic modifications occur over hours, but enable retrograde communication within minutes once AMPA receptor (AMPAR) blockade is removed, causing elevation of both spontaneous and evoked vesicle fusion. The retrograde signaling does not require spiking activity and can be interrupted by NBQX, philanthotoxin, postsynaptic BAPTA, or external sequestration of BDNF, consistent with the acute release of retrograde messenger, triggered by postsynaptic Ca 2+ elevation via Ca 2+ -permeable AMPARs.homeostasis | synaptic scaling | calcium signaling | miniature excitatory postsynaptic currents P rolonged perturbations in the level of activity of neuronal circuits initiate major changes in excitatory transmission. Such retuning is generally homeostatic and is proposed to counterbalance other forms of plasticity and to help keep neuronal firing rate within an optimal range for efficient transfer of information (1-3). There is growing agreement about the functional significance of adaptation to inactivity (2, 4), but much uncertainty remains about where and how such adaptation is expressed.The increase in postsynaptic function in response to prolonged inactivity, evident as an increase in the amplitude of unitary synaptic events (miniature excitatory postsynaptic currents, mEPSCs, or minis), is by now well-established (2, 4). The enlargement of mEPSCs is mediated by an accumulation of AMPA receptors (AMPARs) at postsynaptic sites (5-8). Sometimes the increase is attributed to an increase in Ca 2+ -permeable AMPARs that lack GluA2 subunits (7, 9, 10), but in other cases comparable elevations in both GluA1 and GluA2 have been seen (6,8,11,12). Furthermore, adaptation to inactivity induced by postsynaptic blockade may also involve presynaptic changes, reflected by an elevated frequency of mEPSCs and increased vesicular turnover (7,(13)(14)(15)(16).Although evidence is mounting for both pre-and postsynaptic modifications, the fundamental nature of such alterations remains incompletely understood. On one hand, neuronal inactivity causing cellwide changes in transmitter release and receptivity (2) would fit with descriptions of synaptic homeostasis as a global phenomena. This idea is supported by evidence showing that glial cells can serve as general activity sensors and modulate all synapses in an area (17). On the other hand, findings of tight coordination between closely neighboring synapses (18) and of differential regulation of different types...

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“…Because a single postsynaptic cell contains inputs from multiple neurons, inhibited synapses (SYNYFP plus TNTCFP) should be surrounded by actively releasing presynaptic terminals originating from untransfected neurons (detected by endogenous synapsin). To test the validity of this system, the authors demonstrated that terminals positive for SYNYFP and TNTCFP contain lower levels of VAMP2, suggesting that TNTCFP was indeed functional [Harms et al (2005), their Fig. 1 (http:// www.jneurosci.org/cgi/content/full/25/ 27/6379/FIG1)].…”

mentioning

confidence: 99%