PMID- 28186166
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20200902
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 8
DP  - 2017 Feb 10
TI  - Selective molecular impairment of spontaneous neurotransmission modulates 
      synaptic efficacy.
PG  - 14436
LID - 10.1038/ncomms14436 [doi]
LID - 14436
AB  - 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.
FAU - Crawford, Devon C
AU  - Crawford DC
AUID- ORCID: 0000-0002-9354-4976
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, Texas 75390, 
      USA.
FAU - Ramirez, Denise M O
AU  - Ramirez DM
AD  - Whole Brain Microscopy Facility, Department of Neurology and Neurotherapeutics, 
      UT Southwestern Medical Center, Dallas, Texas 75390, USA.
FAU - Trauterman, Brent
AU  - Trauterman B
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, Texas 75390, 
      USA.
FAU - Monteggia, Lisa M
AU  - Monteggia LM
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, Texas 75390, 
      USA.
FAU - Kavalali, Ege T
AU  - Kavalali ET
AD  - Department of Neuroscience, UT Southwestern Medical Center, Dallas, Texas 75390, 
      USA.
AD  - Department of Physiology, UT Southwestern Medical Center, Dallas, Texas 75390, 
      USA.
LA  - eng
GR  - F32 MH102915/MH/NIMH NIH HHS/United States
GR  - R01 MH066198/MH/NIMH NIH HHS/United States
GR  - R01 MH070727/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170210
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Qb-SNARE Proteins)
RN  - 0 (R-SNARE Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Vamp7 protein, rat)
RN  - 0 (Vti1a protein, rat)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.7.11.20 (Elongation Factor 2 Kinase)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Elongation Factor 2 Kinase/genetics/metabolism
MH  - Female
MH  - Glutamic Acid/*metabolism
MH  - Male
MH  - Mice, Knockout
MH  - Neurons/metabolism/*physiology
MH  - Qb-SNARE Proteins/genetics/metabolism
MH  - R-SNARE Proteins/genetics/metabolism
MH  - RNA Interference
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Synapses/*physiology
MH  - Synaptic Transmission/*physiology
PMC - PMC5311059
COIS- The authors declare no competing financial interests.
EDAT- 2017/02/12 06:00
MHDA- 2018/11/27 06:00
PMCR- 2017/02/10
CRDT- 2017/02/11 06:00
PHST- 2016/05/09 00:00 [received]
PHST- 2016/12/29 00:00 [accepted]
PHST- 2017/02/11 06:00 [entrez]
PHST- 2017/02/12 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2017/02/10 00:00 [pmc-release]
AID - ncomms14436 [pii]
AID - 10.1038/ncomms14436 [doi]
PST - epublish
SO  - Nat Commun. 2017 Feb 10;8:14436. doi: 10.1038/ncomms14436.