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

Yoav Ben-Simon, Alma Rodenas-Ruano, Karina Alviña, Alice D. Lam, Edward L. Stuenkel, Pablo E. Castillo, Uri Ashery

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Neurotransmitter release probability (P<inf>r</inf>) 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<inf>r</inf> 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<inf>r</inf>, 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.

Original languageEnglish (US)
Pages (from-to)396-404
Number of pages9
JournalCell Reports
Volume12
Issue number3
DOIs
StatePublished - Jul 21 2015

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Optogenetics
Neuronal Plasticity
Synapses
Plasticity
Long-Term Potentiation
Cyclic AMP-Dependent Protein Kinases
Fibers
Hippocampal Mossy Fibers
SNARE Proteins
Proteins
Pyramidal Cells
Neurons
Neurotransmitter Agents
Transmitters
Light

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity. / Ben-Simon, Yoav; Rodenas-Ruano, Alma; Alviña, Karina; Lam, Alice D.; Stuenkel, Edward L.; Castillo, Pablo E.; Ashery, Uri.

In: Cell Reports, Vol. 12, No. 3, 21.07.2015, p. 396-404.

Research output: Contribution to journalArticle

Ben-Simon, Y, Rodenas-Ruano, A, Alviña, K, Lam, AD, Stuenkel, EL, Castillo, PE & Ashery, U 2015, 'A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity', Cell Reports, vol. 12, no. 3, pp. 396-404. https://doi.org/10.1016/j.celrep.2015.06.037
Ben-Simon, Yoav ; Rodenas-Ruano, Alma ; Alviña, Karina ; Lam, Alice D. ; Stuenkel, Edward L. ; Castillo, Pablo E. ; Ashery, Uri. / A Combined Optogenetic-Knockdown Strategy Reveals a Major Role of Tomosyn in Mossy Fiber Synaptic Plasticity. In: Cell Reports. 2015 ; Vol. 12, No. 3. pp. 396-404.
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