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Cell Rep. 2015 Jul 21;12(3):396-404. doi: 10.1016/j.celrep.2015.06.037. Epub 2015 Jul 9.

A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity.

Author information

1
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.
2
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA.
3
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
4
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, NY 10461, USA. Electronic address: pablo.castillo@einstein.yu.edu.
5
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.

Abstract

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.

PMID:
26166572
PMCID:
PMC4525481
DOI:
10.1016/j.celrep.2015.06.037
[Indexed for MEDLINE]
Free PMC Article

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