TY - JOUR
T1 - A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity
AU - Ben-Simon, Yoav
AU - Rodenas-Ruano, Alma
AU - Alviña, Karina
AU - Lam, Alice D.
AU - Stuenkel, Edward L.
AU - Castillo, Pablo E.
AU - Ashery, Uri
N1 - Funding Information:
This work was supported by the Israel Science Foundation Grant 730/11 (U.A.), the Binational Science Foundation (BSF) (2009279 to U.A. and P.E.C.), and NIH grants MH081935 and DA017392 to P.E.C., and NS053978 to E.S. and U.A. A.R.-R. was partially supported by a Ford Foundation Fellowship, and K.A. was supported by NIH-T32 NS007439. We thank Drs. Inna Slutsky, Ofer Yizhar, and Thomas Younts for their helpful comments on the manuscript and Dr. Irit Gottfried for assistance throughout this work.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/7/21
Y1 - 2015/7/21
N2 - Neurotransmitter release probability (Pr) 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 Pr 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 Pr, 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 attomosyn-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.
AB - Neurotransmitter release probability (Pr) 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 Pr 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 Pr, 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 attomosyn-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.
UR - http://www.scopus.com/inward/record.url?scp=84937523187&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2015.06.037
DO - 10.1016/j.celrep.2015.06.037
M3 - Article
C2 - 26166572
AN - SCOPUS:84937523187
SN - 2211-1247
VL - 12
SP - 396
EP - 404
JO - Cell Reports
JF - Cell Reports
IS - 3
ER -