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Projection-specific intersectional optogenetics for precise excitation and inhibition in the marmoset brain.

Overview

Authors: Luke Shaw1, Krishnan Padmanabhan1, Amy Bucklaew1, Jude F. Mitchell2, Kuan Hong Wang1
ORCID iDs: Kuan Hong Wang
  1. Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester Medical Center, Rochester, NY 14642, USA
  2. Department of Brain and Cognitive Sciences, University of Rochester, Rochester, NY 14611, USA
Institutions: University of Rochester Medicine (United States); University of Rochester (United States)
Journal: Cell reports methods, volume 6, issue 4, article 101368
Dates: received 18 August 2025; accepted 23 February 2026; published online 30 March 2026; in print April 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1016/j.crmeth.2026.101368 · PMID 41916301 · PMCID PMC13107054 · OpenAlex W7143323478
Open access: gold, a free copy (OpenAlex)
Status: code on request (how the code is found and verified)
Categories: non-human primate (organism), systems (subfield)
Methods: Spectral & time-frequency, Preprocessing, Smoothing, state filtering, decompositions, Evoked potentials, Single-unit activity, calcium imaging, Physiology & signal measures, Connectivity
Keywords: optogenetics, marmoset, Cre-intersection, projection-specific, aav, inhibition, excitation, retrograde labeling, Dlx-enhancer, laminar recording
MeSH: Brain*, Neural Inhibition*, Optogenetics*, Animals, Callithrix, Dependovirus, Integrases, Male, Neurons (* major topic)
Topic: Photoreceptor and optogenetics research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: national institutes of health (P50HD103536, 5R01EY030998-05)
Citations: cited by 4 papers (Europe PMC); 93 references in the paper
Research resources: Mouse Anti-GFP Monoclonal RRID:AB_218216, Mouse Anti-GAD67 clone 1G10.2 RRID:AB_2278725, Rabbit Anti-Cre Recombinase Polyclonal RRID:AB_2549717, RRID:AB_2938133, Mouse: C57BL/6J RRID:IMSR_JAX:000664

Abstract

The primate cerebral cortex relies on long-range connections to integrate information across spatially distributed and functionally specialized areas, yet tools for selectively modulating these pathways remain limited. Here, we present an optimized intersectional viral and optogenetic strategy for precisely exciting and inhibiting projection-specific neurons in the common marmoset. Building on a mouse-to-marmoset pipeline, we first validated that optogenetic activation of inhibitory neurons (via AAV9-mDlx-ChR2) enables robust local cortical inhibition. We then combined retrograde delivery of Cre-recombinase (AAVretro-Cre) with locally injected Cre-dependent vectors encoding excitatory or inhibitory opsins (AAV8-FLEx-ChR2 or Jaws) to achieve directionally selective expression in callosal and frontoparietal pathways. Dual-opsin co-expression enabled precise stimulation or suppression of projection neurons in vivo with minimal off-target labeling. These results establish a scalable framework for projection-specific optogenetic interrogation of distributed circuits in primates, expanding the experimental toolkit for causal studies of higher-order brain function with enhanced anatomical precision and functional specificity.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

Datasets cited

Data and code availability

• Representative electrophysiological data and down-sampled histological image data corresponding to each main figure have been deposited at Zenodo as (Zenodo: 10.5281/zenodo.18643885 (https://doi.org/10.5281/zenodo.18643885)). They are publicly available as of the date of publication. Complete datasets reported in this paper will be shared by the lead contact upon request. • All original code corresponding to each main figure has been deposited at Zenodo and is publicly available at (Zenodo: 10.5281/zenodo.18643885 (https://doi.org/10.5281/zenodo.18643885)) as of the date of publication. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 10 keywords, 9 MeSH terms, 1 funder, 91 references, 5 RRIDs.

Cite

This paper

Shaw, L., Padmanabhan, K., Bucklaew, A., Mitchell, J. F., & Wang, K. H. (2026). Projection-specific intersectional optogenetics for precise excitation and inhibition in the marmoset brain. Cell reports methods, 6(4), 101368. https://doi.org/10.1016/j.crmeth.2026.101368

BibTeX

@article{shaw2026projection,
author = {Shaw, Luke and Padmanabhan, Krishnan and Bucklaew, Amy and Mitchell, Jude F. and Wang, Kuan Hong},
title = {{Projection-specific intersectional optogenetics for precise excitation and inhibition in the marmoset brain}},
journal = {Cell reports methods},
year = {2026},
month = mar,
volume = {6},
number = {4},
pages = {101368},
publisher = {Elsevier},
issn = {2667-2375},
doi = {10.1016/j.crmeth.2026.101368},
url = {https://doi.org/10.1016/j.crmeth.2026.101368},
pmid = {41916301},
pmcid = {PMC13107054}
}

RIS

TY - JOUR
AU - Shaw, Luke
AU - Padmanabhan, Krishnan
AU - Bucklaew, Amy
AU - Mitchell, Jude F.
AU - Wang, Kuan Hong
TI - Projection-specific intersectional optogenetics for precise excitation and inhibition in the marmoset brain
T2 - Cell reports methods
J2 - Cell Rep Methods
PY - 2026
DA - 2026/03/30
VL - 6
IS - 4
SP - 101368
SN - 2667-2375
PB - Elsevier
DO - 10.1016/j.crmeth.2026.101368
UR - https://doi.org/10.1016/j.crmeth.2026.101368
LA - en
ER -

CSL-JSON

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