Glutamate Receptor Expression Regulates Quantal Size and Quantal Content at the<i>Drosophila</i>Neuromuscular Junction

DiAntonio, Aaron; Petersen, Sophie A; Heckmann, Manfred; Goodman, Corey S.

doi:10.1523/jneurosci.19-08-03023.1999

Cited by 286 publications

(455 citation statements)

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(73 reference statements)

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“…The frequency of spontaneous synaptic potentials (similar to vertebrate miniature end-plate potentials) is a widely used measure of synaptic function (11,(47)(48)(49)(50)(51) and scales with membrane excitability. Elevated spontaneous release is also characteristic of other activity mutants with reduced K ϩ currents (46).…”

Section: Sdn Expression Enhances Neuronal Excitabilitymentioning

confidence: 99%

Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K ⁺ channel subunit

Mosca

Carrillo

White

et al. 2005

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

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During nervous system development, synapses undergo morphological change as a function of electrical activity. In Drosophila, enhanced activity results in the expansion of larval neuromuscular junctions. We have examined whether these structural changes involve the pre-or postsynaptic partner by selectively enhancing electrical excitability with a Shaker dominant-negative (SDN) potassium channel subunit. We find that the SDN enhances neurotransmitter release when expressed in motoneurons, postsynaptic potential broadening when expressed in muscles and neurons, and selectively suppresses fast-inactivating, Shaker-mediated I A currents in muscles. SDN expression also phenocopies the canonical behavioral phenotypes of the Sh mutation. At the neuromuscular junction, we find that activity-dependent changes in arbor size occur only when SDN is expressed presynaptically. This finding indicates that elevated postsynaptic membrane excitability is by itself insufficient to enhance presynaptic arbor growth. Such changes must minimally involve increased neuronal excitability.activity ͉ behavioral genetics ͉ Drosophila E lectrical activity plays a prominent role in the development and plasticity of synapses (1-3). The glutamatergic neuromuscular junction (NMJ) of Drosophila is favorable for examining synaptogenesis and the role of electrical activity in synaptic growth and refinement (4, 5). In Drosophila, activity influences synaptic connectivity (6), size (7-9), and homeostasis (10, 11). Activity may also regulate retrograde signals that influence NMJ development (12)(13)(14). However, determining the relative contributions of pre-and postsynaptic excitability to synaptic development remains a significant challenge.Addressing this problem requires molecular tools that selectively alter excitability on either side of the synapse. Early success in suppressing excitability has involved the targeted expression of modified ion channels or receptors (10,15,16). A promising approach for enhancing electrical activity involves the dominantnegative suppression of K ϩ currents involved in membrane repolarization and excitability (17, 18).The Shaker (Sh) type I A K ϩ current of Drosophila plays a key role in regulating membrane excitability of neurons and muscles (19,20) and also influences the processing of graded potentials (21). Sh mutants have well characterized hyperactive behavioral and electrophysiological phenotypes (20,(22)(23)(24), making Sh a good candidate for dominant-negative suppression. Hyperexcitable Sh mutants, when combined with other K ϩ channel mutants such as ether-a-go-go, also have enlarged larval NMJs (7-9). However, whether these structural changes arise from pre-or postsynaptic membrane hyperexcitability has remained unresolved, because the Sh mutation affects both neurons and muscle.To dissect these changes, we have developed a Sh dominantnegative (SDN) transgene as a tool for targeted enhancement of electrical excitability. SDN effectively suppresses I A, as demonstrated by voltage-clamp analysis of muscle...

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Section: Sdn Expression Enhances Neuronal Excitabilitymentioning

confidence: 99%

Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K ⁺ channel subunit

Mosca

Carrillo

White

et al. 2005

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

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“…Also, in the mollusc Helisoma, acquisition of excitation-secretion machinery at nerve-muscle synapses involves activity-dependent signaling through the postsynaptic receptors (Poyer and Zoran, 1996). Finally, at Drosophila neuromuscular synapses, the postsynaptic glutamate receptor regulates quantal size and quantal content of developing presynaptic terminals (DiAntonio et al, 1999). Although all of the above experiments point to the importance of retrograde signals in presynaptic events, direct tests for a role of postsynaptic receptors in altering developmental acquisition of presynaptic release machinery have been hampered by the lack of ACh receptor (AChR) null animal model systems.…”

Section: Introductionmentioning

confidence: 99%

Optical Measurements of Presynaptic Release in Mutant Zebrafish Lacking Postsynaptic Receptors

Ono

Brehm

2003

J. Neurosci.

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Differentiation of presynaptic nerve terminals is mediated, in part, through contact with the appropriate postsynaptic target cell. In particular, studies using dissociated nerve and muscle derived from Xenopus embryos have indicated that the properties of transmitter release from motor neurons are altered after contact with skeletal muscle. This maturation of presynaptic function has further been linked to retrograde signaling from muscle that involves activation of postsynaptic ACh receptors. Using FM1-43 optical determinants of exocytosis, we now compare calcium-mediated exocytosis at neuromuscular junctions of wild-type zebrafish to mutant fish lacking postsynaptic ACh receptors. In response to either high-potassium depolarization or direct electrical stimulation, we observed no differences in the rate or extent of FM1-43 destaining. These data indicate that the acquisition of stimulus-evoked exocytosis at early developmental stages occurs independent of both postsynaptic receptor and synaptic responses in zebrafish.

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“…The change in mEJC amplitude without a change in mEJC frequency is supportive of a postsynaptic effect. Importantly, smaller mEJC amplitudes and faster mEJC decay times occur when B-Class GluRs are expressed exclusively, or when these receptors are present in greater relative abundance (DiAntonio et al, 1999;.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, the synaptic functional changes likely result from this increase in B-class relative to A-class receptors, reflecting differences in A-class and B-class GluR properties. In particular, it has been shown that B-class receptors desensitize much more rapidly than A-class receptors based on analysis of currents in outside-out patches from GluRIIA and GluRIIB knockout animals (DiAntonio et al 1999). If B-class receptor desensitization is regulated through a calcium-dependent mechanism, this could explain the increased EJC amplitudes in lower calcium with no amplitude changes in higher calcium.…”

Section: B-class Glutamate Receptors Are Specifically Regulated By Thmentioning

confidence: 99%

“…A-class GluR abundance has been shown to increase with heightened synaptic activity (Sigrist et al, 2002;Sigrist et al, 2003). Increasing expression of the GluRIIA subunit results in an increase in the amplitude of spontaneous synaptic potentials while over-expression of GluRIIB results in a decrease in the amplitude of spontaneous synaptic potentials (DiAntonio et al, 1999). This suggests that B-class GluRs may be important in fine tuning synaptic responsiveness, but during periods of heightened synaptic activity, they may be rapidly turned over via the UPS and replaced by more stable, slowly desensitizing A-class receptors.…”

Section: B-class Glutamate Receptors Are Specifically Regulated By Thmentioning

confidence: 99%

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The ubiquitin–proteasome system postsynaptically regulates glutamatergic synaptic function

Haas

Miller

Friedman

et al. 2007

Molecular and Cellular Neuroscience

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The ubiquitin proteasome system (UPS) actively controls protein dynamics and local abundance via regulated protein degradation. This study investigates UPS roles in the regulation of postsynaptic function and molecular composition in the Drosophila neuromuscular junction (NMJ) genetic system. To specifically impair UPS function postsynaptically, the UAS/GAL4 transgenic method was employed to drive postsynaptic expression of proteasome β2 and β6 subunit mutant proteins, which operate through a dominant negative mechanism to block proteasome function. When proteasome mutant subunits were constitutively expressed, excitatory junctional current (EJC) amplitudes were increased, demonstrating that postsynaptic proteasome function limits neurotransmission strength. Interestingly, the alteration in synaptic strength was calcium-dependent and miniature EJCs had significantly smaller mean amplitudes and more rapid mean decay rates. Postsynaptic levels of the Drosophila PSD-95/SAP97 homologue, discs large (DLG), and the GluRIIB-containing glutamate receptor were increased, but GluRIIA-containing receptors were unaltered. With acute postsynaptic proteasome inhibition using an inducible transgenic system, neurotransmission was similarly elevated with the same specific increase in postsynaptic GluRIIB abundance. These findings demonstrate postsynaptic proteasome regulation of glutamatergic synaptic function that is mediated through specific regulation of GluRIIB-containing glutamate receptors.

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Glutamate Receptor Expression Regulates Quantal Size and Quantal Content at theDrosophilaNeuromuscular Junction

Cited by 286 publications

References 50 publications

Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K ⁺ channel subunit

Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K ⁺ channel subunit

Optical Measurements of Presynaptic Release in Mutant Zebrafish Lacking Postsynaptic Receptors

The ubiquitin–proteasome system postsynaptically regulates glutamatergic synaptic function

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Glutamate Receptor Expression Regulates Quantal Size and Quantal Content at theDrosophilaNeuromuscular Junction

Cited by 286 publications

References 50 publications

Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K + channel subunit

Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K + channel subunit

Optical Measurements of Presynaptic Release in Mutant Zebrafish Lacking Postsynaptic Receptors

The ubiquitin–proteasome system postsynaptically regulates glutamatergic synaptic function

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Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K ⁺ channel subunit

Dissection of synaptic excitability phenotypes by using a dominant-negative Shaker K ⁺ channel subunit