The Blackbox One provides unprecedented access to mammalian nervous system function by recording voluntary rodent behaviors from below. Paired with the Palmreader machine learning software platform, it offers objective and highly sensitive insights into investigational interventions while reducing animal use. Moreover, it enables high-throughput in vivo experimentation, uncovering behavioral features and nervous system readouts that were previously unseen. With its ability to record from below at high spatial and temporal resolution in a dark and observer-free environment, the Blackbox One, along with the Palmreader software, introduces a new era of neuroscience discovery and drug development.