Optimal photostimulation selection for iterative activity maps

All-optical two-photon holographic optogenetics enables causal circuit mapping by stimulating defined neurons or ensembles while imaging population activity.

Yet exhaustive connectivity mapping remains experimentally prohibitive because of combinatorial complexity, tissue heating, photodamage, and experimental time.

We present OPhELIA (Optimal Photostimulation sElection for Iterative Activity maps), a Bayesian framework for selecting informative perturbations under limited trial budgets.

OPhELIA combines Beta-Bernoulli connectivity inference with an ambiguity-based acquisition heuristic and learned priors derived from pre-stimulation neural activity, augmenting active learning and compressed sensing.

In standalone simulations and in vivo larval zebrafish visuomotor experiments, OPhELIA with active learning improves trial-efficient approximation of exhaustive functional connectomes.

In combinatorial in vivo experiments, OPhELIA with compressed sensing most closely recovers an exhaustive connectome using only 5% of trials.

These results establish OPhELIA as a sample-efficient framework for causal connectomics.