BlueBerry: Closed-loop wireless optogenetic manipulation in freely moving animals

Optogenetics is a powerful approach for linking neural activity to behavior by enabling precise manipulation of defined neuronal populations. Recent advances in wireless technologies have led to remotely controlled optogenetic devices that facilitate the study of more complex behaviors, including social interactions. However, implementing real-time, automated, closed-loop experiments in large-scale, naturalistic environments and in groups of interacting animals remains challenging. Moreover, many existing devices are difficult to reproduce, requiring specialized engineering expertise or fabrication facilities that are not widely available. Here we introduce BlueBerry (www.OptoBlueBerry.org), a lightweight (1.4 g), battery powered, multi-channel wireless optogenetic device that is openly available for the scientific community and can be assembled entirely from off-the-shelf-components. BlueBerry combines robust long-range wireless communication with flexible control of stimulation parameters, making it particularly suited for behavior-triggered optogenetic experiments in large arenas and in multiple freely interacting animals. We demonstrate that BlueBerry can not only guide decision making during large-scale navigation, but also deliver individually controlled, behavior-triggered optogenetic stimulation to multiple freely interacting mice, enabling modulation of social dynamics in real-time. The open availability, modular design, and straightforward integration with existing behavioral frameworks make BlueBerry a practical and scalable tool for systems neuroscience.