PMID- 26166572
OWN - NLM
STAT- MEDLINE
DCOM- 20160512
LR  - 20181113
IS  - 2211-1247 (Electronic)
VI  - 12
IP  - 3
DP  - 2015 Jul 21
TI  - A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in 
      Mossy Fiber Synaptic Plasticity.
PG  - 396-404
LID - S2211-1247(15)00649-X [pii]
LID - 10.1016/j.celrep.2015.06.037 [doi]
AB  - Neurotransmitter release probability (P(r)) largely determines the dynamic 
      properties of synapses. While much is known about the role of presynaptic 
      proteins in transmitter release, their specific contribution to synaptic 
      plasticity is unclear. One such protein, tomosyn, is believed to reduce P(r) by 
      interfering with the SNARE complex formation. Tomosyn is enriched at hippocampal 
      mossy fiber-to-CA3 pyramidal cell synapses (MF-CA3), which characteristically 
      exhibit low P(r), strong synaptic facilitation, and pre-synaptic protein kinase A 
      (PKA)-dependent long-term potentiation (LTP). To evaluate tomosyn's role in 
      MF-CA3 function, we used a combined knockdown (KD)-optogenetic strategy whereby 
      presynaptic neurons with reduced tomosyn levels were selectively activated by 
      light. Using this approach in mouse hippocampal slices, we found that 
      facilitation, LTP, and PKA-induced potentiation were significantly impaired at 
      tomosyn-deficient synapses. These findings not only indicate that tomosyn is a 
      key regulator of MF-CA3 plasticity but also highlight the power of a combined 
      KD-optogenetic approach to determine the role of presynaptic proteins.
CI  - Copyright (c) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Ben-Simon, Yoav
AU  - Ben-Simon Y
AD  - Department of Neurobiology, Wise Faculty of Life Sciences, Tel Aviv University, 
      Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel 
      Aviv 69978, Israel.
FAU - Rodenas-Ruano, Alma
AU  - Rodenas-Ruano A
AD  - Dominick P. Purpura Department of Neuroscience, Albert Einstein College of 
      Medicine, Bronx, New York, NY 10461, USA.
FAU - Alvina, Karina
AU  - Alvina K
AD  - Dominick P. Purpura Department of Neuroscience, Albert Einstein College of 
      Medicine, Bronx, New York, NY 10461, USA.
FAU - Lam, Alice D
AU  - Lam AD
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI 48109, USA.
FAU - Stuenkel, Edward L
AU  - Stuenkel EL
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI 48109, USA.
FAU - Castillo, Pablo E
AU  - Castillo PE
AD  - Dominick P. Purpura Department of Neuroscience, Albert Einstein College of 
      Medicine, Bronx, New York, NY 10461, USA. Electronic address: 
      pablo.castillo@einstein.yu.edu.
FAU - Ashery, Uri
AU  - Ashery U
AD  - Department of Neurobiology, Wise Faculty of Life Sciences, Tel Aviv University, 
      Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel 
      Aviv 69978, Israel. Electronic address: uriashery@gmail.com.
LA  - eng
GR  - T32 NS007439/NS/NINDS NIH HHS/United States
GR  - MH081935/MH/NIMH NIH HHS/United States
GR  - R01 DA017392/DA/NIDA NIH HHS/United States
GR  - R01 NS053978/NS/NINDS NIH HHS/United States
GR  - R01 MH081935/MH/NIMH NIH HHS/United States
GR  - NS053978/NS/NINDS NIH HHS/United States
GR  - DA017392/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150709
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (R-SNARE Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (STXBP5 protein, human)
SB  - IM
MH  - Animals
MH  - Gene Knockdown Techniques/methods
MH  - Humans
MH  - Mice
MH  - Mossy Fibers, Hippocampal/metabolism/*physiology
MH  - Nerve Tissue Proteins/genetics/metabolism/*physiology
MH  - Neuronal Plasticity/*physiology
MH  - Optogenetics/methods
MH  - R-SNARE Proteins/genetics/metabolism/*physiology
MH  - RNA, Small Interfering/*metabolism
PMC - PMC4525481
MID - NIHMS704993
EDAT- 2015/07/15 06:00
MHDA- 2016/05/14 06:00
PMCR- 2015/08/05
CRDT- 2015/07/14 06:00
PHST- 2014/05/27 00:00 [received]
PHST- 2015/05/21 00:00 [revised]
PHST- 2015/06/09 00:00 [accepted]
PHST- 2015/07/14 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/05/14 06:00 [medline]
PHST- 2015/08/05 00:00 [pmc-release]
AID - S2211-1247(15)00649-X [pii]
AID - 10.1016/j.celrep.2015.06.037 [doi]
PST - ppublish
SO  - Cell Rep. 2015 Jul 21;12(3):396-404. doi: 10.1016/j.celrep.2015.06.037. Epub 2015 
      Jul 9.