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Eberle, M. R.

Publications and source records attributed to Eberle, M. R..

3 recordsLinked to original sources

ABEL: an active-learning behavior estimation and labeling platform

Detailed behavior analysis is essential for thorough characterization of ethologically relevant behaviors in model organisms, yet manual annotation of the full behavioral repertoire remains subjective, time intensive, and susceptible to observer error. Advances in machine learning have enabled high-throughput pose estimation on recorded video, but tools for behavior classification from pose and video data are still developing. Instead of hand-scoring every frame of video, experimenters can instead label a small subset of video frames and software trained through machine learning makes predictions on the rest. Here, we present an Active-learning Behavior Estimation and Labeling (ABEL) platform that uses clip-level active learning (i.e., human labeling of short video snippets) with multimodal features (pose, video, context/ROI) to train robust behavior classifiers. We rigorously validated ABEL-derived behavior predictions against expert human observers and field-standard automated software, across diverse rodent behavioral assays. Across eight assays and 45 behaviors, model training required 19.5 hours of human annotation in total, with the reviewer scoring ~8% of available video. Models trained in ABEL achieved a mean precision-recall area under the curve (PR-AUC - a 0-1 score of how well a model balances missed detections against false alarms, with 1 being perfect) of 0.90 (SD 0.09, range 0.60-0.99), with no association between performance and behavior prevalence (r = 0.20). This was aided by custom tools, Essence Extractor and UMAP Interactive Selection, for targeted discovery of high probability clips which reduce the clip review needed to find a rare behavior 6-fold relative to random sampling and 10-fold relative to labeling whole videos. As a biological validation, we assessed how ABEL-derived behaviors relate to underlying neuronal calcium dynamics. Behavior labels were tightly synced with neuronal signatures distinct from ambiguous behavior and randomly chosen, behavior-unrelated time windows (shuffle control). Together, these data indicate that ABEL provides an efficient platform for frame-precise classification of distinct ethologically relevant behaviors.

neuroscience↗

Selective dysregulation of serotonin dynamics in the anterior cingulate cortex and central amygdala following binge alcohol consumption

Serotonin (5HT) is a critical modulator of brain function and behavior that is dysregulated in alcohol use disorder (AUD). The anterior cingulate cortex (ACC) and central nucleus of the amygdala (CeA) play distinct roles in AUD and undergo functional changes in 5HT signaling following binge drinking, but our understanding of real-time 5HT dynamics in these structures is lacking. We hypothesized that binge drinking would elicit brain-region specific dysfunction in 5HT dynamics during appetitive and aversive stimuli processing. Using fiber photometry with the GRAB5HT sensor, we identified distinct reward and aversion 5HT signaling motifs in the ACC and CeA. Consumption of alcohol and other tastants elicited a suppression of GRAB5HT signal in the ACC and an increase in 5HT signal in the CeA. In contrast, aversive stimuli similarly increased 5HT in both structures. The effect of binge drinking on 5HT function was surprisingly non-uniform, producing brain-region, sex-, and stimulus-specific dysfunction in 5HT signaling that dramatically shifted across weeks of alcohol experience. This suggests that adaptations in 5HT signaling are specific to neural circuits underlying discrete functions. Optogenetically stimulating 5HT terminals in the ACC and CeA increased avoidance behavior without being overtly rewarding or aversive, and stimulating 5HT release in the ACC blunted alcohol drinking. Together, these data identify distinct 5HT reward and aversion signaling motifs in the ACC and CeA and highlight early binge drinking as a critical stage of 5HT adaptation and a potential window for therapeutic intervention.

neuroscience↗

Lateral hypothalamus CRFR1 regulation of chronic binge drinking: divergence along anterior-posterior axis

Binge alcohol drinking increases the risk of developing an alcohol use disorder (AUD) and comorbid psychopathology. The lateral hypothalamus (LH) is a brain structure that integrates cognitive and sensory information to tightly regulate motivated behavior, including binge drinking. Importantly, LH function is vulnerable to modulation by the pro-stress neuropeptide corticotropin-releasing factor (CRF), and acute antagonism of CRF receptor 1 (CRFR1) in the LH blunts binge drinking. However, the role of LH CRFR1 in chronic binge drinking is unknown. We used genetically targeted knockdown (KD) of CRFR1 in the LH of male and female mice followed by three weeks of binge drinking using the "Drinking in the Dark" (DID) model. CRFR1 KD in the posterior LH increased alcohol consumption, independent of sex, with no effect of KD in the anterior LH. Consistent with this, total alcohol consumption was negatively correlated with the location of CRFR1 KD in the LH along the anterior-posterior axis. CRFR1 KD did not alter water consumption or body weight, suggesting the effects of CRFR1 KD on alcohol consumption were not due to broad disruption of fluid intake or homeostatic function. In contrast to the observed effects on binge drinking, CRFR1 KD increased anxiety-like behavior and blunted sucrose preference, independent of KD location in the LH. Our findings provide foundational insight into LH function in the context of AUD and prompt further investigation into the divergent roles that distinct circuitry or cell populations along the anterior-posterior axis of the LH may play in binge drinking. HighlightsO_LICRFR1 knockdown in posterior LH increased alcohol drinking independent of sex C_LIO_LIAlcohol intake negatively correlated with AP location of CRFR1 knockdown in LH C_LIO_LICRFR1 knockdown was anxiogenic with more pronounced effects in females C_LIO_LISucrose preference was blunted by CRFR1 knockdown C_LI

neuroscience↗