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Forli, A.

Publications and source records attributed to Forli, A..

3 recordsLinked to original sources

A hippocampal digital Twin reveals latent structure in freely flying bats

Concurrent advances in artificial intelligence (AI), large-scale neuronal recording, and behavioral tracking have enabled increasingly powerful predictive models of brain-behavior relationships. Yet predictive accuracy does not automatically yield interpretable principles of neural organization, particularly during natural behavior, where the relevant variables computed are often unknown in advance. Here, we developed a functional digital twin of the hippocampus, trained jointly on large-scale neural activity and self-directed three-dimensional flight in freely flying bats. A multimodal, multitask transformer accurately predicted both neural activity and behavior, outperformed standard approaches, and generalized across recording sessions. Interrogating the model's representations suggested a form of hippocampal generalization across self-selected trajectories that was not apparent in physical coordinates, but was plainly visible in the model's low-dimensional latent space. We confirmed this organization directly in the recorded neural activity: neurons fired at corresponding stages of spatially distinct paths connecting the same origin and destination, preserving their relative firing order even as their firing fields shifted with the path. Analysis of neuron-specific readouts further identified functional relationships among neurons that generalized from flight to waking rest and sleep, brain states never used for training, and differed systematically between the hippocampal subregions CA1 and CA3. Together, these results show how AI-based functional digital twins can complement conventional analysis by generating testable hypotheses about neural organization during natural behavior.

neuroscience↗

Ultrafast Frame-Free Imaging of Neural Activity with Event Cameras

Frame-based fluorescence imaging has long defined how neural activity is optically measured. This approach requires acquiring all pixels within an image, regardless of whether they carry meaningful neural dynamics, thereby intrinsically coupling spatial and temporal resolution while increasing data output. Here, we introduce an entirely different, frame-free approach that leverages the sparse nature of neural activity using event-based cameras, which asynchronously report fluorescence changes as spatiotemporal events. Compared with a frame-based camera, our method preserves signal fidelity while eliminating the fixed trade-off between spatial resolution, temporal resolution and data rate, thereby reducing data output by orders of magnitude. Applied to hippocampal preparations we demonstrate that the frame-free approach can resolve both single action potentials and fast network dynamics over large fields of view at kilohertz rates, enabling scalable, ultrafast optical recordings.

neuroscience↗

Extended field-of-view ultrathin microendoscopes for high-resolution two-photon imaging with minimal invasiveness in awake mice

Imaging neuronal activity with high and homogeneous spatial resolution across the field-of-view (FOV) and limited invasiveness in deep brain regions is fundamental for the progress of neuroscience, yet is a major technical challenge. We achieved this goal by correcting optical aberrations in gradient index lens-based ultrathin ([≤] 500 {micro}m) microendoscopes using aspheric microlenses generated through 3D-microprinting. Corrected microendoscopes had extended FOV (eFOV) with homogeneous spatial resolution for two-photon fluorescence imaging and required no modification of the optical set-up. Synthetic calcium imaging data showed that, compared to uncorrected endoscopes, eFOV-microendoscopes led to improved signal-to-noise ratio and more precise evaluation of correlated neuronal activity. We experimentally validated these predictions in awake head-fixed mice. Moreover, using eFOV-microendoscopes we demonstrated cell-specific encoding of behavioral state-dependent information in distributed functional subnetworks in a primary somatosensory thalamic nucleus. eFOV-microendoscopes are, therefore, small-cross-section ready-to-use tools for deep two-photon functional imaging with unprecedentedly high and homogeneous spatial resolution.

neuroscience↗