Spontaneous and Evoked Glutamate Release Activates Two Populations of NMDA Receptors with Limited Overlap

Atasoy, Deniz; Ertunç, Mert; Moulder, Krista L.; Blackwell, Justin; Chung, ChiHye; Su, Jianzhong; Kavalali, Ege T.

doi:10.1523/jneurosci.2432-08.2008

Cited by 170 publications

(210 citation statements)

References 73 publications

(112 reference statements)

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“…The probability of spontaneous fusion of a docked vesicle (in the readily releasable pool) is reported to be 0.002–0.006 per second per vesicle (about one in 200 each second) 77, 78, 79, 80. Release in the absence of an action potential can in principal either be intrinsically spontaneous or alternatively it can be triggered by a spontaneous rise in local Ca 2+ .…”

Section: Quantitative Considerationsmentioning

confidence: 99%

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Hypothesis – buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission

et al. 2017

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Neural networks are optimized to detect temporal coincidence on the millisecond timescale. Here, we offer a synthetic hypothesis based on recent structural insights into SNAREs and the C2 domain proteins to explain how synaptic transmission can keep this pace. We suggest that an outer ring of up to six curved Munc13 ‘MUN’ domains transiently anchored to the plasma membrane via its flanking domains surrounds a stable inner ring comprised of synaptotagmin C2 domains to serve as a work‐bench on which SNAREpins are templated. This ‘buttressed‐ring hypothesis’ affords straightforward answers to many principal and long‐standing questions concerning how SNAREpins can be assembled, clamped, and then released synchronously with an action potential.

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Section: Quantitative Considerationsmentioning

confidence: 99%

“…This happens at a rate of 0.012–0.033 s −1 at a typical central synaptic bouton 77, 78, 79, 80. Considering there are ~ 5 release ready (‘primed’) SV per bouton and, in our model, six SNAREpins per SV, the rate of spontaneous release of a single SNAREpin from its clamp is estimated to be 4 × 10 −4 –1.1 × 10 −3 s ‐1 .…”

Section: Figure A1mentioning

confidence: 99%

Hypothesis – buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission

et al. 2017

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“…To confirm the increase in vesicular turnover, we turned to miniature EPSCs generated by postsynaptic NMDA receptors (33). We chose recording conditions that favor NMDA currents (10 μM glycine, no Mg 2+ , and elevated extracellular Ca 2 ), and used template-based detection (34) (Fig.…”

Section: Nmdar Minis Monitor Unitary Synaptic Activity and Verify An mentioning

confidence: 99%

“…Given that spontaneous minis and evoked release may not arise from the same pool of synaptic vesicles (33,36,37), we wanted to know whether evoked release was also increased after blocking of synaptic transmission. Here we monitor vesicle turnover by measuring the fluorescence increase of VGLUT1-pHluorin (38) when the interior of the acidified vesicle comes in contact with the pH neutral external medium.…”

Section: Increase In Evoked Transmission Following Cessation Of Amparmentioning

confidence: 99%

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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“…It has been found that the spontaneous and evoked forms of glutamatergic activity may utilize distinct signaling pathway [10,11] . It is possible that NMDAR blockade would initiate a different signaling pathway that depends on spontaneous activity.…”

mentioning

confidence: 99%

Blocking NMDA receptor at rest: a possible alleviation of depression

Lü

2011

Acta Pharmacol Sin

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Spontaneous and Evoked Glutamate Release Activates Two Populations of NMDA Receptors with Limited Overlap

Abstract: In a synapse, spontaneous and action-potential-driven neurotransmitter release is assumed to activate the same set of postsynaptic receptors. Here, we tested this assumption using (ϩ)-5-methyl-10,11-dihydro-5H-dibenzo

Cited by 170 publications

References 73 publications

Hypothesis – buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission

Hypothesis – buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission

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

Blocking NMDA receptor at rest: a possible alleviation of depression

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