Single-Cell Perturbations Reveal Selective Modulation of Causal Connectivity During Decision-Making

Ioffe, M.; Thiberge, S. Y.; Brody, C.; Tank, D. W.

doi:10.64898/2026.04.07.716761

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bioRxiv · 10.64898/2026.04.07.716761

Single-Cell Perturbations Reveal Selective Modulation of Causal Connectivity During Decision-Making

Ioffe, M.·Thiberge, S. Y.·Brody, C.·Tank, D. W.

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Abstract

How does cortical connectivity support decision-making? Behavioral tasks often involve multiple sequential phases that implement different computations. For perceptual decision-making during navigation these can include evidence accumulation, decision commitment, and motor program read out. How are these different phases implemented in circuits with fixed anatomical synaptic connectivity? One potential contribution is that the connectivity of neurons is modulated in the different phases, but this has never been tested. Here we used an all-optical method to probe the causal connectivity of excitatory neurons in layer 2/3 of mouse retrosplenial cortex during different behavioral epochs of a navigation-based decision-making task, as well as in the absence of the task. In-task connectivity was different from no-task connectivity: furthermore, these differences were selective to the cue / decision phase, tapering off in later stages of the task. We propose that fast modulation of connectivity is a prevalent mechanism in neural circuit function.

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Ioffe, M., Thiberge, S. Y., Brody, C., Tank, D. W.. 2026-04-08. Single-Cell Perturbations Reveal Selective Modulation of Causal Connectivity During Decision-Making. https://doi.org/10.64898/2026.04.07.716761

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