Biology subjects

Marks, L. C.

Publications and source records attributed to Marks, L. C..

4 recordsLinked to original sources

bioRxiv2026

Psilocybin collapses visual change detection and drives cortical dynamics toward a state of surprise

Psilocybin profoundly alters visual perception, yet the neuronal mechanisms underlying these effects remain unclear. Here we combined large-scale Neuropixels recordings with cell-type specific optogenetics in head-fixed mice performing a visual change-detection task. Psilocybin severely impaired task performance without overt motor deficits. In cortex, the drug modestly suppressed activity of layer 5 neurons while preserving representations of image identity. By contrast, psilocybin imposed a 4-Hz oscillation on visually evoked activity that preferentially affected neurons encoding image change rather than image identity. Under psilocybin, expected image repetitions aberrantly recruited change-encoding ensembles and shifted cortical population dynamics towards trajectories normally evoked by genuine stimulus changes. These effects were strongest in somatostatin-expressing (SST) interneurons in visual cortex. The strength of this modulation depended on image structure and was greatest for images with clear, continuous contours, which preferentially recruited change-encoding ensembles. These findings demonstrate that psilocybin drives internally generated cortical surprise signals, providing a circuit mechanism for altered perception in the acute psychedelic state.

neuroscience↗

bioRxiv2026

Brain-wide reconfiguration of burst firing by psilocybin reveals 5-HT2A-dependent circuit dynamics

Psilocybin produces rapid and lasting therapeutic effects, yet how 5-HT2A receptor activation reshapes brain-wide circuit dynamics during acute drug administration remains poorly understood. Using simultaneous multi-region Neuropixels recordings of 46,360 single units from 35 mice, together with scalp electroencephalography (EEG), pupillometry, and locomotion monitoring, we provide a brain-wide, single-unit and field-potential characterization of psilocybin's acute effects, with pharmacological dissection using the 5-HT2A antagonist ketanserin. Psilocybin selectively reconfigured burst coding, rather than mean firing rate, across cortical, thalamic, and hippocampal circuits: burst firing decreased in hippocampal CA1-CA3 and was bidirectionally modulated in the thalamus, with the reticular nucleus bursting more and first-order geniculate nuclei bursting less. Critically, most of these burst effects were abolished by ketanserin, consistent with at least partial 5-HT2A receptor dependence. These data suggest that the psychedelic state is not simply a matter of how much neurons fire, but of how they fire, pointing to a region-specific, 5-HT2A-associated reconfiguration of burst coding that may underlie the acute phenomenology of the psilocybin experience.

neuroscience↗

bioRxiv2026

Pupil-DLC: an open-source deep learning pipeline for scalable, markerless tracking of pupil dynamics across conscious and unconscious states

BackgroundPupil diameter is a non-invasive biomarker of brain state, correlating with arousal, attention, cognitive processing, and consciousness. However, existing pupillometry software often lacks scalability and robustness across diverse experimental conditions and species. New methodWe introduce Pupil-DLC, an open-source, offline, DeepLabCut-based pipeline for scalable, marker-less pupil tracking, primarily designed for mice. Trained on 21,750 manually annotated frames from over 140 videos of head-fixed mice spanning wakefulness and drug-induced states, including psychedelics and anesthesia, the dataset was deliberately selected to maximize pupil size variability and model generalization. Pupil-DLC implements a dual-model architecture: a General Model (GM) for high-throughput analysis and an Individual Model (IM) for session-specific optimization. ResultsPupil-DLC captures pupil dynamics across awake, psychedelic, and anesthetized conditions with high agreement with ground truth and equal tracking fidelity during active locomotion and quiet rest. Confidence metrics aligned with human frame quality assessments, enabling principled tuning of accuracy-retention trade-offs. As a secondary demonstration, Pupil-DLC extends to unseen human videos across diverse conditions and frame rates, including daylight and smartphone recordings, without retraining. Comparison with existing methodsPupil-DLC outperforms existing automated methods in accuracy and frame retention while maintaining computational efficiency comparable to real-time tools. These improvements stem from a learned keypoint-based representation robust to pupil shape variability, occlusions, reflections, and imaging artifacts. The GM/IM framework supports a tiered strategy balancing throughput and precision. ConclusionsPupil-DLC provides a reproducible, adaptable platform for quantifying pupil-linked brain state dynamics across experimental paradigms and species, bridging basic mouse neuroscience and translational human applications.

neuroscience↗

bioRxiv2022

Cortico-thalamo-cortical interactions modulate electrically evoked EEG responses in mice

Perturbational complexity analysis predicts the presence of consciousness in volunteers and patients by stimulating the brain with brief pulses, recording electroencephalographic (EEG) responses, and computing their spatiotemporal complexity. We examined the underlying neural circuits in mice by directly stimulating cortex while recording with EEG and Neuropixels probes during wakefulness and isoflurane anesthesia. When mice are awake, stimulation of deep cortical layers reliably evokes locally a brief pulse of excitation, followed by a bi-phasic sequence of 120 ms profound off period and a rebound excitation. A similar pattern, partially attributed to burst spiking, is seen in thalamic nuclei, and is associated with a pronounced late component in the evoked EEG. We infer that cortico-thalamo-cortical interactions drive the long-lasting evoked EEG signals elicited by deep cortical stimulation during the awake state. The cortical and thalamic off period and rebound excitation, and the late component in the EEG, are reduced during running and absent during anesthesia.

neuroscience↗