Evidence map›Paper›PMID 33846537›Full record

ArticleCommunications biology2021

An engineered channelrhodopsin optimized for axon terminal activation and circuit mapping.

Shun Hamada, Masashi Nagase, Tomohiko Yoshizawa, Akari Hagiwara, Yoshikazu Isomura, Ayako M Watabe, Toshihisa Ohtsuka

Open access · goldAbstract read
In one paragraph

Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.8field-weighted citation impact, top 17% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Temporally Coordinated Activity among Motor Cortex, Thalamus, and Thalamic Reticular Nucleus Neurons during Rat Forelimb Movements.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026
    Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Protein design accelerates the development and application of optogenetic tools.Computational and structural biotechnology journal · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Beyond a Transmission Cable-New Technologies to Reveal the Richness in Axonal Electrophysiology.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Optogenetics at the presynapse.Nature neuroscience · 2022
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Shun Hamada *Department of Biochemistry, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.ORCID 0000-0002-8928-5385
Masashi Nagase *Institute of Clinical Medicine and Research, Research Center for Medical Sciences, The Jikei University School of Medicine, Chiba, Japan.
Tomohiko Yoshizawa *Department of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.ORCID 0000-0001-6232-5941
Akari Hagiwara *Department of Biochemistry, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.ORCID 0000-0001-6470-6641
Yoshikazu IsomuraDepartment of Physiology and Cell Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan. isomura.phy2@tmd.ac.jp.ORCID 0000-0003-0393-3124
Ayako M WatabeInstitute of Clinical Medicine and Research, Research Center for Medical Sciences, The Jikei University School of Medicine, Chiba, Japan. awatabe@jikei.ac.jp.ORCID 0000-0002-6916-5757
Toshihisa OhtsukaDepartment of Biochemistry, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan. tohtsuka@yamanashi.ac.jp.ORCID 0000-0002-1566-1325
University of Yamanashi · JPJikei University School of Medicine · JPTokyo Medical and Dental University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Optogenetic tools such as channelrhodopsin-2 (ChR2) enable the manipulation and mapping of neural circuits. However, ChR2 variants selectively transported down a neuron's long-range axonal projections for precise presynaptic activation remain lacking. As a result, ChR2 activation is often contaminated by the spurious activation of en passant fibers that compromise the accurate interpretation of functional effects. Here, we explored the engineering of a ChR2 variant specifically localized to presynaptic axon terminals. The metabotropic glutamate receptor 2 (mGluR2) C-terminal domain fused with a proteolytic motif and axon-targeting signal (mGluR2-PA tag) localized ChR2-YFP at axon terminals without disturbing normal transmission. mGluR2-PA-tagged ChR2 evoked transmitter release in distal projection areas enabling lower levels of photostimulation. Circuit connectivity mapping in vivo with the Spike Collision Test revealed that mGluR2-PA-tagged ChR2 is useful for identifying axonal projection with significant reduction in the polysynaptic excess noise. These results suggest that the mGluR2-PA tag helps actuate trafficking to the axon terminal, thereby providing abundant possibilities for optogenetic experiments.

Indexed as

AnimalsChannelrhodopsinsFemaleMiceMice, Inbred C57BLOptogeneticsPresynaptic TerminalsProtein EngineeringReceptors, Metabotropic GlutamateChannelrhodopsinsmetabotropic glutamate receptor 2Receptors, Metabotropic Glutamate

Identifiers

PMID33846537
PMCPMC8042110
OpenAlexW3156419555

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.