Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy

Devon C. Crawford, Denise M O Ramirez, Brent Trauterman, Lisa M Monteggia, Ege T Kavalali

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Recent studies suggest that stimulus-evoked and spontaneous neurotransmitter release processes are mechanistically distinct. Here we targeted the non-canonical synaptic vesicle SNAREs Vps10p-tail-interactor-1a (vti1a) and vesicle-associated membrane protein 7 (VAMP7) to specifically inhibit spontaneous release events and probe whether these events signal independently of evoked release to the postsynaptic neuron. We found that loss of vti1a and VAMP7 impairs spontaneous high-frequency glutamate release and augments unitary event amplitudes by reducing postsynaptic eukaryotic elongation factor 2 kinase (eEF2K) activity subsequent to the reduction in N-methyl-D-aspartate receptor (NMDAR) activity. Presynaptic, but not postsynaptic, loss of vti1a and VAMP7 occludes NMDAR antagonist-induced synaptic potentiation in an intact circuit, confirming the role of these vesicular SNAREs in setting synaptic strength. Collectively, these results demonstrate that spontaneous neurotransmission signals independently of stimulus-evoked release and highlight its role as a key regulator of postsynaptic efficacy.

Original languageEnglish (US)
Article number14436
JournalNature Communications
Volume8
DOIs
StatePublished - Feb 10 2017

Fingerprint

R-SNARE Proteins
impairment
Synaptic Transmission
aspartates
SNARE Proteins
membranes
N-Methyl-D-Aspartate Receptors
proteins
stimuli
Elongation Factor 2 Kinase
neurotransmitters
glutamates
Synaptic Vesicles
regulators
neurons
elongation
Neurons
Neurotransmitter Agents
Glutamic Acid
Networks (circuits)

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Crawford, D. C., Ramirez, D. M. O., Trauterman, B., Monteggia, L. M., & Kavalali, E. T. (2017). Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy. Nature Communications, 8, [14436]. https://doi.org/10.1038/ncomms14436

Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy. / Crawford, Devon C.; Ramirez, Denise M O; Trauterman, Brent; Monteggia, Lisa M; Kavalali, Ege T.

In: Nature Communications, Vol. 8, 14436, 10.02.2017.

Research output: Contribution to journalArticle

Crawford, DC, Ramirez, DMO, Trauterman, B, Monteggia, LM & Kavalali, ET 2017, 'Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy', Nature Communications, vol. 8, 14436. https://doi.org/10.1038/ncomms14436
Crawford, Devon C. ; Ramirez, Denise M O ; Trauterman, Brent ; Monteggia, Lisa M ; Kavalali, Ege T. / Selective molecular impairment of spontaneous neurotransmission modulates synaptic efficacy. In: Nature Communications. 2017 ; Vol. 8.
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