Retrograde optogenetics reveals sensorimotor convergence within a corticotectal pathway of non-human primates

Understanding how the cerebral cortex communicates with subcortical areas to drive behavior remains a central question in system neuroscience. One key unresolved issue is whether prefrontal cortical outputs to motor-related subcortical regions carry predominantly motor commands<sup>1</sup> or mixed sensory-motor signals.<sup>2</sup><sup>,</sup><sup>3</sup> Retrograde optogenetics offers a powerful way to interrogate such projection-defined circuits,<sup>4</sup><sup>,</sup><sup>5</sup><sup>,</sup><sup>6</sup><sup>,</sup><sup>7</sup> but its use in non-human primates has been limited.<sup>8</sup><sup>,</sup><sup>9</sup><sup>,</sup><sup>10</sup><sup>,</sup><sup>11</sup> Here, we applied retrograde optogenetics in awake macaques to directly test the functional organization of the corticotectal projection from the frontal eye field (FEF) to the superior colliculus (SC). We asked whether the FEF output signals to SC are motor-dominant or broadly sensory-motor. Optical activation of this pathway evoked robust, contralateral saccades and selectively modulated reaction times, demonstrating its causal role in saccade generation. Optogenetically tagging FEF neurons projecting to SC revealed a heterogeneous population of visual, visuomotor, and motor neurons. This diverse output converged predominantly onto motor-related neurons in the SC. These findings support a visuomotor convergence model, in which diverse FEF outputs drive motor-selective SC neurons with activity sufficient for saccade generation, and thus resolve long-standing questions over the composition of FEF outputs. Additionally, our results establish retrograde optogenetics as a tool for dissecting projection-defined circuits in primates and for precisely probing the neural pathways that link perception to action.

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Publication Details

Journal
Current Biology
Published
2025-12-05
DOI
https://doi.org/10.1016/j.cub.2025.11.021
Citations
1
Primary Topic
Photoreceptor and optogenetics research
Type
article
Field-Weighted Citation Impact
0.91
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article

Retrograde optogenetics reveals sensorimotor convergence within a corticotectal pathway of non-human primates

Okihide Hikosaka, Masahiko Takada, Ken‐ichi Inoue, Atul Gopal et al.
1 citations
Current Biology
Photoreceptor and optogenetics research
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article

Retrograde optogenetics reveals sensorimotor convergence within a corticotectal pathway of non-human primates

Okihide Hikosaka, Masahiko Takada, Ken‐ichi Inoue, Atul Gopal, Xuefei Yu, Martin O. Bohlen, Hendrikje Nienborg, Marc A. Sommer, Genevieve M. Kuczewski
article en
1 citations

Abstract

Understanding how the cerebral cortex communicates with subcortical areas to drive behavior remains a central question in system neuroscience. One key unresolved issue is whether prefrontal cortical outputs to motor-related subcortical regions carry predominantly motor commands<sup>1</sup> or mixed sensory-motor signals.<sup>2</sup><sup>,</sup><sup>3</sup> Retrograde optogenetics offers a powerful way to interrogate such projection-defined circuits,<sup>4</sup><sup>,</sup><sup>5</sup><sup>,</sup><sup>6</sup><sup>,</sup><sup>7</sup> but its use in non-human primates has been limited.<sup>8</sup><sup>,</sup><sup>9</sup><sup>,</sup><sup>10</sup><sup>,</sup><sup>11</sup> Here, we applied retrograde optogenetics in awake macaques to directly test the functional organization of the corticotectal projection from the frontal eye field (FEF) to the superior colliculus (SC). We asked whether the FEF output signals to SC are motor-dominant or broadly sensory-motor. Optical activation of this pathway evoked robust, contralateral saccades and selectively modulated reaction times, demonstrating its causal role in saccade generation. Optogenetically tagging FEF neurons projecting to SC revealed a heterogeneous population of visual, visuomotor, and motor neurons. This diverse output converged predominantly onto motor-related neurons in the SC. These findings support a visuomotor convergence model, in which diverse FEF outputs drive motor-selective SC neurons with activity sufficient for saccade generation, and thus resolve long-standing questions over the composition of FEF outputs. Additionally, our results establish retrograde optogenetics as a tool for dissecting projection-defined circuits in primates and for precisely probing the neural pathways that link perception to action.

Current BiologyVol. 36(1)
National Institutes of Health (US), Duke University (US), Kyoto University (JP), Nagoya City University (JP), National Eye Institute (US)
Openalex Percentile: Top 19%
Photoreceptor and optogenetics research
0.91
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