Biology subjects

Datta, S. R.

Publications and source records attributed to Datta, S. R..

At least 19 recordsLinked to original sources

bioRxiv2026

Spontaneous behavior predicts colony membership, individual identity, and rank in naked mole-rat societies

Animal societies are organized across scales, from moment-to-moment actions of individuals to dynamic group structure. A central challenge in sociobiology is to understand how behaviors of individuals shape group structure. Here, using machine vision to map recurrent fine-scale behavioral modules in the eusocial naked mole-rat (Heterocephalus glaber), we show that spontaneous behavior in isolation predicts group-level social organization, including colony membership and individual identity. We determined dominance relationships and found highly linear hierarchies, with ranks stable over months to years. Remarkably, fine-scale behavioral profiles in isolation correctly predicted pairwise dominance relationships, allowing reconstruction of rank order within each colony. Models trained within one colony predicted rank poorly in others, suggesting that naked mole-rats express social position through behavioral patterns specific to each colony. Together, our results connect fine-scale behavior to social structure maintained over years and show that, even when an animal is alone, its behavior carries signatures of its identity, colony, and place within that society.

animal behavior and cognition↗

bioRxiv2026

Inferring the evolving objectives that organize animal behavior

Understanding how the brain supports flexible, goal-directed behavior is a central aim of neuroscience. Yet such behavior is highly variable and unfolds over long timescales, making it challenging to understand its organization. Advances in behavioral tracking quantify movements but do not reveal the objectives that guide them. Motivated by this, we develop inverse reinforcement learning (IRL) into a general framework for inferring these objectives from naturalistic behavior. Our approach represents an animal's objectives as internal rewards, and infers these rewards as well as the policies they induce from observed behavior. It applies across diverse behavioral settings, from freely moving behaviors to structured tasks. It can infer objectives that switch over time or gradually change with experience. In mice capturing crickets, it identified a small set of objectives that the animals switched between over the course of a trial. In mice learning a cued labyrinth, it inferred how the animals' internal rewards changed as learning progressed. Across both datasets, the models predicted held-out actions and generated extended behavior that reproduced key features of animal performance. By transforming long, variable behavioral sequences into time-resolved estimates of the animal's objectives, our approach provides a quantitative basis for studying how the brain organizes natural behavior.

neuroscience↗

bioRxiv2026

TEX15 safeguards neuronal diversity in the mouse olfactory system

Animals detect diverse chemicals using hundreds of chemoreceptor proteins. In many organisms, sensory chemoreceptors obey a one-receptor-type-per-cell rule, which organizes information gathered by sensory neurons. A key question remains how receptor expression gets diversified so that hundreds of chemoreceptors get expressed across the population of sensory neurons. Here we show that diverse odorant receptor (OR) expression in mice requires testis expressed gene 15 (Tex15). We find that Tex15 regulates OR expression in neuronal precursor cells. In Tex15 deficient (Tex15-/-) mice, OR transcript levels are increased in precursors, a handful of early-transcribed OR genes get expressed at abnormally high levels, and these ORs come to dominate the olfactory sensory neuron population. This results in a profound reduction in the diversity of OR gene choice as well as disrupted spatial patterning of the olfactory epithelium, without disrupting the one-receptor-type-per-cell rule. Tex15 encodes a transcriptional repressor, and we show that Tex15-/- mice have reduced heterochromatin-associated H3K9me3 on OR genes. Thus, we propose that Tex15 directs a heterochromatin-based transcriptional repression mechanism that prevents uneven transcriptional onset from skewing OR choice. This mechanism safeguards the cellular diversity that is essential for broadly tuned chemosensation.

genomics↗

bioRxiv2025

Altered striatal dopamine dynamics and behavior in Grin2a mutant mice, a genetic mouse model of schizophrenia

Schizophrenia (SCZ), a complex psychiatric disorder with a strong genetic basis, is thought to involve, at least in part, dopamine dysregulation in the striatum. Recent large-scale exome sequencing has identified multiple SCZ risk genes, including GRIN2A (encoding an NMDA (N-methyl-D-aspartate) receptor subunit) and AKAP11 (encoding a protein kinase A binding protein), which is also a risk gene for bipolar disorder (BD). However, the mechanisms by which these genetic risk factors perturb dopamine circuits and cause psychotic symptoms remain poorly understood. We asked how behavior, dorsomedial striatal dopamine (DA) dynamics and the activity of D1-/D2-spiny projection neurons (SPNs) were altered in Grin2a and Akap11 mutants. In the open field, Grin2a knockout mice display hyperlocomotion and an abnormal organization of naturalistic behaviors. They also displayed heightened behavioral responses to objects and auditory stimuli. Grin2a heterozygous animals mostly showed intermediate phenotypes, suggesting a dose-dependent effect of Grin2a loss. Further, Grin2a knockout mutants exhibited aberrant dopamine events, altered coupling of dopamine with locomotor features, and exaggerated stimuli-evoked dopamine responses. Notably, heterozygous animals also showed altered striatal SPN events in the open field reflecting dysregulated neural activity in both dSPNs and iSPNs. Compared to Grin2a mutants, Akap11 mutants displayed opposite phenotypes, showing reduced locomotion with a shift from high- to low-velocity movement and distinct alterations in striatal neural activity. Together, GRIN2A (SCZ risk) and AKAP11 (BD/SCZ risk) mutations induce different, often opposite, effects on striatal dopamine signaling and behavior, suggesting that these two risk genes act through distinct mechanisms.

neuroscience↗

bioRxiv2025

Spectral envelopes of rhythmic facial movements predict intention and motor cortical representations

1Animals, including humans, use coordinated facial movements to sample the environment, ingest nutrients, and communicate. Rodents, in particular, produce rhythmic facial movements during spontaneous behavior and cognitive tasks. Measuring these movements precisely and linking them to neural activity remains challenging. We introduce face-rhythm, an unsupervised pipeline that combines markerless pointtracking, spectral analysis, and non-negative tensor component analysis to decompose facial video into a small set of interpretable components. Applied to videos of mice during a Pavlovian odor-reward task, a brain-machine interface (BMI) task, and free behavior, face-rhythm recovers human-interpretable behaviors such as whisking, sniffing, licking, and subtler motifs. The resulting components are consistent across animals, are sufficient to decode task variables or internal belief states, and explain cortical activity using a low-rank representation. We also find that the activity of neurons in face-associated primary motor cortex (M1) is predicted well by a phase-invariant spectral transformation of facial movements above [~]0.5 Hz, while slower movements retain a phase-variant representation better predicted by the instantaneous position of the face; individual neurons can show either or both forms of tuning. A systematic comparison against deeplearning point-tracking models, contrastive-learning embeddings, and vision-transformer features places face-rhythm competitively across tasks while also achieving the goal of producing a low-dimensional, interpretable description of rodent facial behavior that is closely linked to cortical activity.

neuroscience↗

bioRxiv2025

A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain

Although topographical maps organize many peripheral sensory systems, it remains unclear whether olfactory sensory neurons (OSNs) choose which of the [~]1100 odor receptors (ORs) to express based upon their spatial location in the olfactory epithelium (OE) or instead ORs are scattered randomly. Here we reveal that each OR is expressed at a precise mean position along the OE dorsoventral axis, thereby instantiating a receptor map. This patterning reflects the differential use, by precursors and mature OSNs, of a coherent gene expression program controlled by a spatially-varying retinoic acid gradient; this program -- which includes key transcription factors and axon guidance genes -- translates position into a spatially appropriate distribution of OR choices and aligns the epithelial map of OR identity with the glomerular map present in the olfactory bulb. These results identify a transcriptional code that distinguishes and spatially organizes the vast array of sensory channels that comprise the olfactory system.

neuroscience↗

bioRxiv2024

Concerted modulation of spontaneous behavior and time-integrated whole-brain neuronal activity by serotonin receptors

Serotonin neurons from the raphe nuclei project across the entire brain and modulate diverse physiology and behavior by acting on over a dozen receptors. Here, we took a step towards dissecting this complex process by examining the effects of agonists and antagonists of four widely expressed serotonin receptors (2A, 2C, 1A, and 1B) on spontaneous mouse behavior, which we related to time-integrated whole-brain neuronal activity as assessed by the expression of Fos, a canonical immediate-early gene product. Low-dimensional representations of behavioral and Fos map data revealed the dominant factors of variation in each domain, captured predictable differences across drug groups, and enabled predictions of behavioral changes following perturbations in Fos maps and vice versa. Our study provides a rich resource describing the effects of manipulating serotonin receptors on animal behavior and whole-brain integrated neuronal activity. It also establishes an experimental and analysis paradigm for interrogating the relationship between behavior and neuronal activity across different time scales.

neuroscience↗

bioRxiv2024

Behavioral fingerprinting of the naked mole-rat uncovers signatures of eusociality and social touch

The East African naked mole-rat (Heterocephalus glaber) lives in cooperative subterranean colonies and displays a capacity to recognize social novelty, rank, and identity. The sensory cues used for social recognition remain poorly understood, especially because many of their senses are either lost or greatly reduced in comparison to other mammals. Here, we found that naked mole-rats actively touch faces 100% of the time they encounter one another in a tunnel test, followed by milliseconds speed determination of the rank of the other animal. Even in an open arena, naked mole-rats engage in face-to-face touch hundreds of times in a 10-minute social pairing and colonies do so tens of thousands of times over a 24-hour period in their home environment. To demonstrate the prominence of face touch at a molecular level, we show that social housing conditions lead to widespread activation of mechanosensory ion channels, including Piezo2, in neurons that innervate the face, but not the body. Lastly, to determine the ethological relevance of face touch, we reduced its capacity with facial whisker trimming and revealed an apparent inability for animals to recognize colony members. Together, these findings uncover face touch as a prominent social behavior in naked mole-rats that is intimately linked to social recognition.

neuroscience↗

bioRxiv2024

Dynamics of striatal action selection and reinforcement learning

Spiny projection neurons (SPNs) in dorsal striatum are often proposed as a locus of reinforcement learning in the basal ganglia. Here, we identify and resolve a fundamental inconsistency between striatal reinforcement learning models and known SPN synaptic plasticity rules. Direct-pathway (dSPN) and indirect-pathway (iSPN) neurons, which promote and suppress actions, respectively, exhibit synaptic plasticity that reinforces activity associated with elevated or suppressed dopamine release. We show that iSPN plasticity prevents successful learning, as it reinforces activity patterns associated with negative outcomes. However, this pathological behavior is reversed if functionally opponent dSPNs and iSPNs, which promote and suppress the current behavior, are simultaneously activated by efferent input following action selection. This prediction is supported by striatal recordings and contrasts with prior models of SPN representations. In our model, learning and action selection signals can be multiplexed without interference, enabling learning algorithms beyond those of standard temporal difference models.

neuroscience↗

bioRxiv2023

Using behavioral biomarkers to redefine epochs of spontaneous recovery following spinal cord injury

The brain-spinal cord axis generates movement by assembling motor primitives into coordinated sequences. Spinal cord injury (SCI) disrupts this neuroaxis, impairing not only locomotion, but the full repertoire of behavior. Traditional scales for quantifying recovery collapse this complexity into predefined locomotor-focused criteria that obscure heterogeneity in recovery. To quantify the full behavioral repertoire following SCI, we adapted motion sequencing (MoSeq) to identify sub-second behavioral "syllables" and capture their usage and sequential organization without predefined features. We identified biomechanically distinct variants within syllable classes that are shared across injury severities and found that recovery is jointly structured by injury severity and individual mouse identity. Changes in sequences, however, unfold along a conserved temporal trajectory. By compressing behavior into a single metric, we uncovered clusters of coevolving locomotor and non-locomotor behaviors. These results frame SCI recovery with repertoire-level changes, where adaptive strategies emerge from constrained access to motor primitives and their sequences.

neuroscience↗

bioRxiv2023

Metabotropic signaling within somatostatin interneurons regulates thalamocortical inputs during development

During brain development, neural circuits undergo major activity-dependent restructuring. Circuit wiring mainly occurs through synaptic strengthening following the Hebbian "fire together, wire together" precept. However, select connections, essential for circuit development, are transient. They are effectively connected early in development, but strongly diminish during maturation. The mechanisms by which transient connectivity recedes are unknown. To investigate this process, we characterize transient thalamocortical inputs, which depress onto somatostatin inhibitory interneurons during development, by employing optogenetics, chemogenetics, transcriptomics and CRISPR-based strategies. We demonstrate that in contrast to typical activity-dependent mechanisms, transient thalamocortical connectivity onto somatostatin interneurons is non-canonical and involves metabotropic signaling. Specifically, metabotropic-mediated transcription, of guidance molecules in particular, supports the elimination of this connectivity. Remarkably, we found that this developmental process impacts the development of normal exploratory behaviors of adult mice.

neuroscience↗

bioRxiv2023

Mammalian olfactory cortex neurons retain molecular signatures of ancestral cell types

The cerebral cortex diversified extensively during vertebrate evolution. Intriguingly, the three-layered mammalian olfactory cortex resembles the cortical cytoarchitecture of non-mammals yet evolved alongside the six-layered neocortex, enabling unique comparisons for investigating cortical neuron diversification. We performed single-nucleus multiome sequencing across mouse three- to six-layered cortices and compared neuron types across mice, reptiles and salamander. We identified neurons that are olfactory cortex-specific or conserved across mouse cortical areas. However, transcriptomically similar neurons exhibited area-specific epigenetic states. Additionally, the olfactory cortex showed transcriptomic divergence between lab and wild-derived mice, suggesting enhanced circuit plasticity through adult immature neurons. Finally, olfactory cortex neurons displayed marked transcriptomic similarities to reptile and salamander neurons. Together, these data indicate that the mammalian olfactory cortex retains molecular signatures representative of ancestral cortical traits.

neuroscience↗

bioRxiv2023

Towards Preclinical Validation of Arbaclofen (R-baclofen) Treatment for 16p11.2 Deletion Syndrome

A microdeletion on human chromosome 16p11.2 is one of the most common copy number variants associated with autism spectrum disorder and other neurodevelopmental disabilities. Arbaclofen, a GABA(B) receptor agonist, is a component of racemic baclofen, which is FDA-approved for treating spasticity, and has been shown to alleviate behavioral phenotypes, including recognition memory deficits, in animal models of 16p11.2 deletion. Given the lack of reproducibility sometimes observed in mouse behavioral studies, we brought together a consortium of four laboratories to study the effects of arbaclofen on behavior in three different mouse lines with deletions in the mouse region syntenic to human 16p11.2 to test the robustness of these findings. Arbaclofen rescued cognitive deficits seen in two 16p11.2 deletion mouse lines in traditional recognition memory paradigms. Using an unsupervised machine-learning approach to analyze behavior, one lab found that arbaclofen also rescued differences in exploratory behavior in the open field in 16p11.2 deletion mice. Arbaclofen was not sedating and had modest off-target behavioral effects at the doses tested. Our studies show that arbaclofen consistently rescues behavioral phenotypes in 16p11.2 deletion mice, providing support for clinical trials of arbaclofen in humans with this deletion. One sentence summaryExperiments across four laboratories found that arbaclofen rescued cognitive deficits in mouse models of 16p11.2 deletion, without sedation or significant off-target behavioral effects.

neuroscience↗

bioRxiv2023

Keypoint-MoSeq: parsing behavior by linking point tracking to pose dynamics

Keypoint tracking algorithms have revolutionized the analysis of animal behavior, enabling investigators to flexibly quantify behavioral dynamics from conventional video recordings obtained in a wide variety of settings. However, it remains unclear how to parse continuous keypoint data into the modules out of which behavior is organized. This challenge is particularly acute because keypoint data is susceptible to high frequency jitter that clustering algorithms can mistake for transitions between behavioral modules. Here we present keypoint-MoSeq, a machine learning-based platform for identifying behavioral modules ("syllables") from keypoint data without human supervision. Keypoint-MoSeq uses a generative model to distinguish keypoint noise from behavior, enabling it to effectively identify syllables whose boundaries correspond to natural sub-second discontinuities inherent to mouse behavior. Keypoint-MoSeq outperforms commonly used alternative clustering methods at identifying these transitions, at capturing correlations between neural activity and behavior, and at classifying either solitary or social behaviors in accordance with human annotations. Keypoint-MoSeq therefore renders behavioral syllables and grammar accessible to the many researchers who use standard video to capture animal behavior.

neuroscience↗

bioRxiv2023

ArMo: An Articulated Mesh Approach for Mouse 3D Reconstruction

Characterizing animal behavior requires methods to distill 3D movements from video data. Though keypoint tracking has emerged as a widely used solution to this problem, it only provides a limited view of pose, reducing the body of an animal to a sparse set of experimenter-defined points. To more completely capture 3D pose, recent studies have fit 3D mesh models to subjects in image and video data. However, despite the importance of mice as a model organism in neuroscience research, these methods have not been applied to the 3D reconstruction of mouse behavior. Here, we present ArMo, an articulated mesh model of the laboratory mouse, and demonstrate its application to multi-camera recordings of head-fixed mice running on a spherical treadmill. Using an end-to-end gradient based optimization procedure, we fit the shape and pose of a dense 3D mouse model to data-derived keypoint and point cloud observations. The resulting reconstructions capture the shape of the animals surface while compactly summarizing its movements as a time series of 3D skeletal joint angles. ArMo therefore provides a novel alternative to the sparse representations of pose more commonly used in neuroscience research.

animal behavior and cognition↗

bioRxiv2022

Brain region-specific changes in neurons and glia and dysregulation of dopamine signaling in Grin2a mutant mice

Schizophrenia disease mechanisms remain poorly understood, in large part due to a lack of valid animal models. Rare heterozygous loss-of-function mutations in GRIN2A, encoding a subunit of the NMDA (N-methyl-d-aspartate) receptor, greatly increase the risk of schizophrenia. By transcriptomic, proteomic, electroencephalogram (EEG) recording and behavioral analysis, we report that heterozygous Grin2a mutant mice show: (i) large-scale gene expression changes across multiple brain regions and in neuronal (excitatory and inhibitory) and non-neuronal cells (astrocytes, oligodendrocytes); (ii) evidence of reduced activity in prefrontal cortex and increased activity in hippocampus and striatum; (iii) elevated dopamine signaling in striatum; (iv) altered cholesterol biosynthesis in astrocytes; (v) reduction of glutamatergic receptor signalin g proteins in the synapse; (iv) heightened gamma oscillation power in EEG; (vi) aberrant locomotor behavioral pattern opposite of that induced by antipsychotic drugs. These findings reveal potential pathophysiologic mechanisms, provide support for both the "hypo-glutamate" and "hyper-dopamine" hypotheses of schizophrenia, and underscore the utility of Grin2a-deficient mice as a new genetic model of schizophrenia.

neuroscience↗

bioRxiv2022

Distinguishing discrete and continuous behavioral variability using warped autoregressive HMMs

A core goal in systems neuroscience and neuroethology is to understand how neural circuits generate naturalistic behavior. One foundational idea is that complex naturalistic behavior may be composed of sequences of stereotyped behavioral syllables, which combine to generate rich sequences of actions. To investigate this, a common approach is to use autoregressive hidden Markov models (ARHMMs) to segment video into discrete behavioral syllables. While these approaches have been successful in extracting syllables that are interpretable, they fail to account for other forms of behavioral variability, such as differences in speed, which may be better described as continuous in nature. To overcome these limitations, we introduce a class of warped ARHMMs (WARHMM). As is the case in the ARHMM, behavior is modeled as a mixture of autoregressive dynamics. However, the dynamics under each discrete latent state (i.e. each behavioral syllable) are additionally modulated by a continuous latent "warping variable." We present two versions of warped ARHMM in which the warping variable affects the dynamics of each syllable either linearly or nonlinearly. Using depth-camera recordings of freely moving mice, we demonstrate that the failure of ARHMMs to account for continuous behavioral variability results in duplicate cluster assignments. WARHMM achieves similar performance to the standard ARHMM while using fewer behavioral syllables. Further analysis of behavioral measurements in mice demonstrates that WARHMM identifies structure relating to response vigor.

animal behavior and cognition↗

bioRxiv2022

Persistent post-COVID-19 smell loss is associated with inflammatory infiltration and altered olfactory epithelial gene expression

Most human subjects infected by SARS-CoV-2 report an acute alteration in their sense of smell, and more than 25% of COVID patients report lasting olfactory dysfunction. While animal studies and human autopsy tissues have suggested mechanisms underlying acute loss of smell, the pathophysiology that underlies persistent smell loss remains unclear. Here we combine objective measurements of smell loss in patients suffering from post-acute sequelae of SARS-CoV-2 infection (PASC) with single cell sequencing and histology of the olfactory epithelium (OE). This approach reveals that the OE of patients with persistent smell loss harbors a diffuse infiltrate of T cells expressing interferon-gamma; gene expression in sustentacular cells appears to reflect a response to inflammatory signaling, which is accompanied by a reduction in the number of olfactory sensory neurons relative to support cells. These data identify a persistent epithelial inflammatory process associated with PASC, and suggests mechanisms through which this T cell-mediated inflammation alters the sense of smell.

neuroscience↗