At Janelia Research Campus, the Howard Hughes Medical Institute is betting on Danionella, a tiny transparent adult fish, combined with artificial intelligence, to map how brain activity drives complex behaviors and social interactions.

Danionella will be used alongside established models like fruit flies and larval zebrafish to validate methods, while tool-building remains a core Janelia strength in microscopes, sensors, connectomes, and computation.

Gerry Rubin notes that Danionella offers brain-wide activity measurement in a fully adult vertebrate, opening new possibilities beyond the group’s past fruit fly successes.

Danionella’s transparency offers imaging advantages over zebrafish, enabling direct visualization of brain activity during natural behaviors such as schooling, navigation, courtship, and social interactions.

The plan seeks a mechanistic, multi-level account of brain function spanning molecules to action, while developing AI-driven discovery processes to interpret data, generate hypotheses, design experiments, and automate steps.

Janelia’s approach leverages its interdisciplinary ecosystem of tool builders, tool users, and AI experts, with a strong emphasis on open sharing of tools, datasets, and methodologies.

The project aims to build a comprehensive brain-connectome for Danionella and create AI-assisted tools to analyze data, enabling experiments in freely swimming fish rather than immobilized specimens.

HHMI leadership frames the Danionella effort as a long-horizon challenge with potential benefits for science and human health, signaling a bold rethinking of how research is conducted.

The initiative represents a strategic shift for Janelia, shifting resources away from some rodent work and related programs toward Danionella to enable large-scale, collaborative neuroscience beyond what individual labs can achieve.

AI-in-the-Loop will analyze results, simulate approaches, design tools, detect patterns, update predictions with new data, and compress discovery timelines from months to days, aligning with HHMI’s broader AI initiatives.

Experts stress that observing the brain in real time within a larger, freely behaving animal is essential to link neural activity to behavior, requiring advances in imaging, data analysis, and engineering to manage massive data loads.

This effort builds on Janelia’s history of large-scale connectomics, aiming to extend these approaches to a vertebrate brain to advance understanding of memory, decision-making, and basic brain-behavior relationships with potential human relevance.