Biology subjects

Watson, B. O.

Publications and source records attributed to Watson, B. O..

13 recordsLinked to original sources

bioRxiv2026

SpikeCleaner: An Algorithm to Label Unit Quality After Automated Spike Sorting

GapAutomated spike sorting algorithms have revolutionized the way neuronal activity is extracted from extracellular recordings, yet they remain imperfect. Specifically, inaccurate acceptance of noise-based units not only leaves researchers with clusters that require extensive manual curation, an essential but time-consuming process, that also leads to significant subjectivity in the selection of units. In an era of high-density probes like Neuropixels, where an hour of data can exceed 80 GB, manual curation is no longer scalable, automation of standard criteria can speed data curation and ensure quality of datasets. Here, we developed a semi-automated curation pipeline to label the quality of units after automated curation by Kilosort. ApproachOur algorithm standardizes criteria for labeling of Noise, Multi-Unit Activity (MUA), and Good Units using a combination of spike rate, spike timing metrics (from autocorrelogram), and waveform-based physiological features such as peak amplitude, slopes, half-width, and inter-channel correlation. Based on these features, clusters are assigned standardized labels (good, noise, multi-unit activity) that can be imported directly into Phy, where they serve as curation aids rather than absolute classifications, supporting but not replacing expert judgment. Heuristically, "noise" units are those unlikely to be neuronal in origin; "MUA" includes units with significant neural contribution (i.e., neuronal waveform) but with some degree of clear imperfection to be further cleaned, and "good" units are those without any clear deviation from ideal unit criteria. By ensuring accurate selection of acceptable units, we enable robust downstream analyses such as neural decoding and longitudinal tracking of neuron identity. Thresholds for all metrics were chosen to maximize the matching of algorithm output to that of 2 expert manual curators. Of note, users may alter thresholds either based on their own judgment or using an included tool to semi-automatically find thresholds that optimize SpikeCleaner with their own expert curation. ResultsTo benchmark, we compared the outputs of our algorithm to expert-labels curated in Phy by two expert users across three recordings. SpikeCleaner achieved an average of 97% accuracy vs. experts & 92% F1 score in classifying Single Units. It achieved an accuracy of 97% & 92% F1 score in full-category agreement (SU, MUA, Noise), and 97% accuracy & 95% F1 score in distinguishing Neuronal vs. Non-Neuronal units.

neuroscience↗

bioRxiv2026

Altered Lighting Conditions Elicit Sex-Specific Circadian Behaviors in Diurnal Grass Rats

Circadian rhythms are crucial to biological functions, and cognitive functions such as attention, choice, and preference-related behaviors are modulated by circadian rhythms and disrupted in mood disorders such as Seasonal Affective Disorder (SAD) and Major Depressive Disorder (MDD). These neuropsychiatric diseases can be induced or worsened by alterations to daily light patterns and can also be treated with circadian-timed bright-light therapy, suggesting modulatory effects of light brightness on mood and behavior. While most laboratory rodents are nocturnal, the Nile grass rat (Arvicanthis niloticus) is diurnal, offering a unique model to study light modulation effects relevant to humans. In this work, we track daily activity in male and female grass rats under varied lighting for several weeks, revealing sex-specific circadian patterns and responses. These findings establish a foundation for mechanistic studies of light effects on mood-related brain circuits in diurnal animals.

neuroscience↗

bioRxiv2025

Neurotype matching in monogamous rodents is modulated by early-life sleep experience

Studies of human sociability indicate stronger social affinity in matched-neurotype dyads (e.g., two individuals with autism or two without) compared to mixed-neurotype dyads (e.g., one individual with autism paired with one without). Is this neurotype matching phenomenon also quantifiable in non-human animals? Using deep learning tools, we analyzed dyadic male-female interactions in prairie voles, a highly social rodent species. To simulate "neurotypes", voles were exposed to either control conditions or early-life sleep disruption (ELSD) during a critical neurodevelopmental period (postnatal days 14-21), recapitulating two features of human autism: developmental sleep disruption and later-life atypical sociability. Analogous to human studies, voles showed signs of reduced social affinity in mixed dyads compared to matched dyads, including sex-specific changes in aggression and body orientation toward the conspecific. These findings advance our understanding of social affinity, providing a framework for new studies in both animal models and humans.

animal behavior and cognition↗

bioRxiv2025

Developmental time course of social touch, parvalbumin interneurons, perineuronal nets and Mef2c expression reveals a sensitive period of somatosensory cortex development in prairie voles

Social touch facilitates our attachment to others, especially early in life, which may be linked to the maturation of parvalbumin interneurons (PVI) in the somatosensory cortex (S1). These neurons respond to social touch, mature in a sensory experience-dependent manner, and influence both somatosensory processing and social behavior in models of Autism Spectrum Disorder. Prairie voles (Microtus ochrogaster) are an ideal rodent model for studying these concepts since they engage in a species-typical social touch called "huddling". This study first showed that over development from juvenile to adult, same-sex siblings huddled less and explored more. Next, we tracked two markers of plasticity indicative of PVI maturation, extracellular perineuronal nets (PNNs) and nuclear transcription factor Myocyte enhancing factor 2C (Mef2c) - across seven developmental timepoints. We found that, while PV expression in S1 was stable by P21, PNNs and Mef2c continued to shift afterwards, indicating a protracted development. Four unique clusters of PVIs converge during development between P14-P21, suggesting a sensitive period of PVI development. Finally, to determine environmental factors affecting these processes, environmental enrichment between P21-P28 led to accelerated PVI maturation. This developmental mapping provides a particularly salient model to investigate the molecular underpinnings of cortical and social development.

neuroscience↗

bioRxiv2025

Mouse Bio-behavioral Phenotyping Using a Digital Homecage Framework for Long-timescale, High-resolution, and Multi-factor Data Collection and Analytics

MOTIVATION Long-term monitoring of behavioral and physiological processes is critical for understanding complex brain-based phenomena and disorders that develop over extended periods, such as chronic stress, circadian disorders, and metabolic conditions. While digital phenotyping is available in humans using smart devices, there remains a deficit in rodent models. To address this lack of long-term rodent phenotyping, we introduce the "Digital Homecage" (DHC) system. Our system uses accessible components and is designed for seamless integration with brain recording technologies. The Digital Homecage (DHC) allows uninterrupted, long-timescale recording of more than 20 behavioral metrics in single-housed mice, captured at sub-second resolution via video, operant interactions, and wheel-running data. This report demonstrates the DHCs capacity to enable continuous, automated tracking of behaviors like actigraphy, sleep, grooming, and food choice options over weeks, thereby opening up new avenues for longitudinal analyses of chronic conditions. Data collected reveal circadian patterns in multiple spontaneous behaviors, aligning with known nocturnal tendencies. The systems potential to facilitate groundbreaking observations on the long-term behavioral correlates of various neuropsychiatric syndromes is aided by open-source software and relatively low cost. The DHC sets the stage for community-driven innovation, potentially transforming our approach to studying complex traits of brain function and behavior in laboratory settings.

animal behavior and cognition↗

bioRxiv2024

Quantifying social roles in multi-animal videos using subject-aware deep-learning

Analyzing social behaviors is critical for many fields, including neuroscience, psychology, and ecology. While computational tools have been developed to analyze videos containing animals engaging in limited social interactions under specific experimental conditions, automated identification of the social roles of freely moving individuals in a multi-animal group remains unresolved. Here we describe a deep-learning-based system - named LabGym2 - for identifying and quantifying social roles in multi-animal groups. This system uses a subject-aware approach: it evaluates the behavioral state of every individual in a group of two or more animals while factoring in its social and environmental surroundings. We demonstrate the performance of subject-aware deep-learning in different species and assays, from partner preference in freely-moving insects to primate social interactions in the field. Our subject-aware deep learning approach provides a controllable, interpretable, and efficient framework to enable new experimental paradigms and systematic evaluation of interactive behavior in individuals identified within a group.

animal behavior and cognition↗

bioRxiv2022

Early-life sleep disruption impairs subtle social behaviors during pair bond formation in prairie voles: A computer vision study

Early life sleep disruption (ELSD) has been shown to have long lasting effects on social behavior in adult prairie voles (Microtus ochrogaster), including impaired expression of pair bond behavior during partner preference testing (e.g., reduced huddling with a pair bonded partner). However, due to the limitations of manual behavior tracking, the behavioral effects of ELSD across the entire time course of pair bond formation have not yet been described, hindering our ability to trace mechanisms. Here, we used computer vision to precisely track multiple behaviors during opposite-sex cohabitation of prairie voles. Male-female pairs were allowed to interact through a mesh divider in the home cage for 72 h, providing variables of body direction, distance-to-divider, and locomotion speed, with temporal resolution as high as the video frame rate (20-25 Hz). We found that control males displayed periodic, stereotyped patterns of body orientation towards females during pair bond formation. In contrast, ELSD males showed reduced duration and ultradian periodicity of these body orientation behaviors towards females. Furthermore, in both sexes, ELSD altered stereotypical spatial and temporal patterns of locomotion seen in control animals that typically varied across days of cohabitation and light/dark periods. This study highlights the utility of computer vision in deep characterization of subtle behaviors and allows a more comprehensive behavioral assessment of the profound and persistent effects of ELSD on later life social behavior. Our findings may shed light on causal mechanisms underlying human neurodevelopmental disorders featuring sleep disruption and social deficits, such as autism spectrum disorder.

animal behavior and cognition↗

bioRxiv2022

3D Printed Skull Cap and Benchtop Fabricated Microwire-based Microelectrode Array for Custom Rat Brain Recordings

Microwire microelectrode arrays (MEAs) have been a popular low-cost tool for chronic electrophysiological recordings. Multi-MEA implantations can reveal electrical dynamics crucial to brain function. However, both the fabrication and implantation procedures for multi-MEAs on a single rodent are time-consuming and highly manual skill-dependent for quality. To enable in-house design, fabrication, and implantation of custom microwire MEAs, we developed (1) a computer-aided designed and 3D printed skull cap for pre-determined implantation locations of each MEA and (2) a benchtop fabrication approach for low-cost custom microwire MEAs. A proof-of-concept design of 32-channel 4-MEA (8-wire each) recording system was prototyped and tested through Sprague Dawley rat recordings. The skull cap design based on CT-scan of single rat conforms well with multiple Sprague Dawley rats of various size, age, and weight with minimal bregma alignment error. The prototyped 32-channel system were able to record spiking activities over 5 months. In comparison with conventional stereotactic surgeries, the skull cap system simplifies the implantation location alignment for each MEA by embedding them into the pre-printed designs, thus dramatically reducing the surgical time and effort and increasing the accuracy and repeatability. Compared to commercially available custom microwire MEAs, this in-house fabrication method enables neuroscience labs to create a custom recording apparatus with lower cost and shorter lead time for design modifications. A new methodology for neuroscience labs to fabricate and insert custom microwire MEAs has been developed and it could be easily generalized to enable low-cost highly-custom multi-region recording/stimulation studies. HighlightsO_LI3D printed skull caps as implantation platform for multi-region rat brain recording C_LIO_LIComputer-aided design for custom cap geometry and predetermined implantation location C_LIO_LIBenchtop microwire fabrication approach for in-house custom microelectrode arrays C_LIO_LIDuplicable and generalizable design, fabrication, and implantation methodologies C_LI

neuroscience↗

bioRxiv2022

REM sleep has minute-scale rhythms in mice and humans: A non-binary continuum between phasic and tonic microstates

Rapid eye movement sleep (REM) is believed to have a binary temporal structure with "phasic" and "tonic" microstates, defined by motoric activity versus quiescence, respectively. However, we observed in mice that the frequency of theta activity (a marker of rodent REM) fluctuates in a non-binary fashion, with the extremes of that fluctuation correlating with phasic-type and tonic-type facial motricity. This demonstrates that phasic and tonic REM rather represent ends of a continuum. These cycles of brain physiology and facial movement occurred at 0.01-0.06 Hz, or infraslow frequencies, and affected cross-frequency coupling and neuronal assembly activity in the neocortex, suggesting network functional impact. We then confirmed that humans also demonstrate non-binary phasic/tonic microstates, with continuous 0.01-0.04 Hz respiratory rate cycles matching the incidence of eye movements. Thus, we discovered a fundamental property of REM, which can yield new insights into our understanding of sleep health.

neuroscience↗

bioRxiv2022

Sleep alterations in a mouse model of Spinocerebellar ataxia type 3

BackgroundSpinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder showing progressive neuronal loss in several brain areas and a broad spectrum of motor and non-motor symptoms, including ataxia and altered sleep. While sleep disturbances are known to play pathophysiologic roles in other neurodegenerative disorders, their impact on SCA3 is unknown. ObjectivesUsing state-of-the art spectrographic measurements, we sought to quantitatively characterize sleep electroencephalography (EEG) in a SCA3 transgenic mouse model with confirmed disease phenotype. MethodsWe first measured motor phenotypes in 18-31-week-old homozygous and hemizygous SCA3 YACMJD84.2 mice and non-transgenic wild-type littermate mice during lights-on and lights-off periods. We next implanted electrodes to obtain 12-hour (zeitgeber time 0-12) EEG recordings for three consecutive days when the mice were 26-36 weeks old. We then analyzed EEG-based sleep structure data to quantify differences between homozygous, hemizygous, and wild-type mice. ResultsCompared to wild-type littermates, SCA3 homozygous mice display: i) increased duration of rapid-eye movement sleep (REM) and fragmentation in all sleep and wake states; ii) higher beta power oscillations during REM and non-REM (NREM); and iii) additional spectral power band alterations during REM and wake. ConclusionsOur data show that sleep architecture and EEG spectral power are dysregulated in homozygous SCA3 mice, indicating that common sleep-related etiologic factors may underlie mouse and human SCA3 phenotypes.

neuroscience↗

bioRxiv2021

Ketamine decreases HPA axis reactivity to a novel stressor in male but not female mice

Ketamine is an antidepressant drug that interacts with the hypothalamic-pituitary-adrenal (HPA) axis, but whether this interaction is important for its behavioral effect is unknown. The goal of this experiment was to determine whether the behavioral response to ketamine depends on intact HPA axis function. Male and female C57BL/6J mice underwent chronic unpredictable stress prior to ketamine (30 mg/kg, i.p.) or vehicle treatment, with or without the glucocorticoid synthesis inhibitor metyrapone (20 mg/kg, i.p.) to block adrenal corticosterone production. Mice were tested in the forced swim test (FST) and open field test one and two days after injection, respectively. Fecal corticosterone was measured at select time points. No significant drug effects on behavior were observed. Males consistently had higher fecal corticosterone levels and stress-induced increases than females. Ketamine lowered the fecal corticosterone response to the FST only in males. These data show that ketamine after chronic stress decreases the corticosterone response to a novel stressor (the FST) in males, but not females. Corticosterone levels in all mice correlated with immobility in the FST, suggesting that shared neural circuitry could mediate both endocrine and behavioral responses. This circuitry may be ketamine-responsive only in males.

animal behavior and cognition↗

bioRxiv2017

Temporal coupling of field potentials and action potentials in the neocortex

The local field potential (LFP) is an aggregate measure of group neuronal activity and is often correlated with the action potentials of single neurons. In recent years investigators have found that action potential firing rates increase during elevations in power high-frequency band oscillations (50-200 Hz range). However action potentials also contribute to the LFP signal itself, making the spike-LFP relationship complex. Here we examine the relationship between spike rates and LFPs in varying frequency bands in rat neocortical recordings. We find that 50-180Hz oscillations correlate most consistently with high firing rates, but that other LFPs bands also carry information relating to spiking, including in some cases anti-correlations. Relatedly, we find that spiking itself and electromyographic activity contribute to LFP power in these bands. The relationship between spike rates and LFP power varies between brain states and between individual cells. Finally, we create an improved oscillation-based predictor of action potential activity by specifically utilizing information from across the entire recorded frequency spectrum of LFP. The findings illustrate both caveats and improvements to be taken into account in attempts to infer spiking activity from LFP.

neuroscience↗

bioRxiv2016

Sleep regulation of the distribution of cortical firing rates

Sleep is thought to mediate mnemonic and homeostatic functions. However, the mechanism by which this brain state can implement both the \"selective\" plasticity needed to consolidate novel memory traces as well as the \"general\" plasticity necessary to maintain a well-functioning neuronal system is unclear. Recent findings show that both of these functions differentially affect neurons based on their intrinsic firing rate, a ubiquitous neuronal heterogeneity. Furthermore, they are both implemented by the NREM slow oscillation, which also distinguishes neurons based on firing rate during sequential activity at the DOWN->UP transition. These findings suggest a mechanism by which spiking activity during the slow oscillation acts to maintain network statistics that promote a skewed distribution of neuronal firing rates, and \"perturbation\" of that activity by hippocampal replay acts to integrate new memory traces into the existing cortical network.

neuroscience↗