Beckerle, T. | bioRxiv Science

bioRxiv2026

Coordinated Representational Drift Across the Mouse Cortex

Cortical neurons continuously change their spatial tuning properties over days and weeks, yet how this representational drift is coordinated across distributed cortical networks remains unknown. Using a robotic cranial exoskeleton for chronic widefield calcium imaging with cellular resolution, we tracked over 110,000 unique layer 2/3 neurons across retrosplenial, visual, somatosensory, and motor cortices in mice navigating a figure-8 maze spanning 47 days. Single-neuron spatial tuning properties followed a posterior-to-anterior gradient, with retros-plenial and visual cortices containing the highest proportions of spatially tuned neurons. This was dissociated from local functional coupling, which was strongest in somatosensory cortex. Population activity formed a low-dimensional manifold whose geometry mirrored the structure of the maze. Despite these regional differences, all four regions decorrelated with similar exponential timescales, and session-specific deviations from each regions decay trajectory were correlated across all pairwise region combinations, suggesting that drift was coordinated rather than independent across the dorsal cortex. This coordination persisted after controlling for shared behavioral fluctuations. Furthermore, drift was consistent with an orthogonal transformation of the population code that preserved the geometric relationships between spatial representations across sessions despite continuous drift in single-neuron tuning.

neuroscience↗

bioRxiv2023

Brain-wide neural recordings in mice navigating physical spaces enabled by a cranial exoskeleton

Complex behaviors are mediated by neural computations occurring throughout the brain. In recent years, tremendous progress has been made in developing technologies that can record neural activity at cellular resolution at multiple spatial and temporal scales. However, these technologies are primarily designed for studying the mammalian brain during head fixation - wherein the behavior of the animal is highly constrained. Miniaturized devices for studying neural activity in freely behaving animals are largely confined to recording from small brain regions owing to performance limitations. We present a cranial exoskeleton that assists mice in maneuvering neural recording headstages that are orders of magnitude larger and heavier than the mice, while they navigate physical behavioral environments. Force sensors embedded within the headstage are used to detect the mouses milli-Newton scale cranial forces which then control the x, y, and yaw motion of the exoskeleton via an admittance controller. We discovered optimal controller tuning parameters that enable mice to locomote at physiologically realistic velocities and accelerations while maintaining natural walking gait. Mice maneuvering headstages weighing up to 1.5 kg can make turns, navigate 2D arenas, and perform a navigational decision-making task with the same performance as when freely behaving. We designed an imaging headstage and an electrophysiology headstage for the cranial exoskeleton to record brain-wide neural activity in mice navigating 2D arenas. The imaging headstage enabled recordings of Ca2+ activity of 1000s of neurons distributed across the dorsal cortex. The electrophysiology headstage supported independent control of up to 4 silicon probes, enabling simultaneous recordings from 100s of neurons across multiple brain regions and multiple days. Cranial exoskeletons provide flexible platforms for largescale neural recording during the exploration of physical spaces, a critical new paradigm for unraveling the brain-wide neural mechanisms that control complex behavior.

neuroscience↗