Biology subjects

Abdus-Saboor, I.

Publications and source records attributed to Abdus-Saboor, I..

17 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

The functional diversification of somatosensory neuron repertoires across Mammalia

The striking diversity of mammalian body forms and surfaces, lifestyles, and habitats prompts the question of how each species' somatosensory neuron repertoire accommodates such diversity. The visual and olfactory systems diversify by gaining and losing sensor/receptor genes and corresponding sensory cell types. Using multiomic single-cell analysis of dorsal root ganglia neurons from thirteen different mammalian species and cross-species functional studies enabled by cell-type-specific enhancer viruses, we show that mammals instead assemble species-specific, functionally distinct somatosensory neuron repertoires from a conserved set of neuron types (orthotypes). Repertoire diversification takes multiple forms: orthotype abundance scales with variable bodily traits like hair follicle density, facilitating relevant behaviors; sensor/receptor expression is shuffled across species, such that orthotypes can detect different stimuli in different species; and orthotypes split into functionally distinct, species-specific subtypes (paratypes). Thus, unlike other sensory systems, the mammalian somatosensory system diversifies through multifarious changes to conserved orthotypes, enabling adaptation to diverse habitats, lifestyles, and body forms.

neuroscience↗

bioRxiv2026

Oxytocin Modulation of Spinal Circuits Drives Therapeutic Benefits of Massage

Across social species, social touch enhances well-being and reduces pain -- two seemingly distinct benefits that enhance survival. Yet where and how the nervous system integrates these functions, and whether a single mechanism could serve both, remains unknown. Here we show that massage triggers oxytocin release, which shapes both pain and touch reward at the earliest stage of central processing -- the spinal cord -- through a single, state-dependent circuit mechanism. We report that in humans, massage enhances well-being, effects that correlate with endogenous oxytocin release. In mice, gentle touch activates hypothalamic oxytocin neurons that project directly to the spinal dorsal horn. Genetic manipulation of spinal oxytocin circuits alters behavioral responses to both gentle touch and noxious stimuli. Spinal calcium imaging and slice electrophysiology reveal that oxytocin acts on both excitatory and inhibitory spinal neurons to sculpt the relative activity of spinal ascending systems that convey both social touch and pain to the brain. Extending these findings to humans, we show that oxytocin receptors are also expressed on spinal excitatory and inhibitory neurons, and that endogenous oxytocin during massage correlates with altered spinal touch processing. Thus, spinal oxytocin signaling provides an evolutionarily conserved mechanism for the therapeutic benefits of massage.

neuroscience↗

bioRxiv2024

Remote automated delivery of mechanical stimuli coupled to brain recordings in behaving mice

The canonical framework for testing pain and mechanical sensitivity in rodents is manual delivery of stimuli to the paw. However, this approach is time consuming, produces variability in results, requires significant training, and is ergonomically unfavorable to the experimenter. To circumvent limitations in manual delivery of stimuli, we have created a device called the ARM (Automated Reproducible Mechano-stimulator). Built using a series of linear stages, cameras, and stimulus holders, the ARM is more accurate at hitting the desired target, delivers stimuli faster, and decreases variability in delivery of von Frey hair filaments. We demonstrate that the ARM can be combined with traditional measurements of pain behavior and automated machine-learning based pipelines. Importantly, the ARM enables remote testing of mice with experimenters outside the testing room. Using remote testing, we found that mice habituated more quickly when an experimenter was not present and experimenter presence leads to significant sex-dependent differences in paw withdrawal and pain associated behaviors. Lastly, to demonstrate the utility of the ARM for neural circuit dissection of pain mechanisms, we combined the ARM with cellular-resolved microendoscopy in the amygdala, linking stimulus, behavior, and brain activity of amygdala neurons that encode negative pain states. Taken together, the ARM improves speed, accuracy, and robustness of mechanical pain assays and can be combined with automated pain detection systems and brain recordings to map central control of pain.

neuroscience↗

bioRxiv2024

The Dorsal Column Nuclei Scales Mechanical Allodynia During Neuropathic Pain

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. Two main drivers of peripheral tactile information, low-threshold mechanoreceptors (LTMRs) and postsynaptic dorsal column neurons (PSDCs), terminate in the brainstem dorsal column nuclei (DCN). Activity within the DRG, spinal cord, and DCN have all been implicated in mediating allodynia, yet the DCN remains understudied at the cellular, circuit, and functional levels compared to the other two. Here, we show that the gracile nucleus (Gr) of the DCN mediates tactile sensitivity for low-threshold stimuli and contributes to mechanical allodynia during neuropathic pain in mice. We found that the Gr contains local inhibitory interneurons in addition to thalamus-projecting neurons, which are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations resulted in bidirectional changes to tactile sensitivity, but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, silencing Gr projection neurons or activating Gr inhibitory neurons was able to reduce tactile hypersensitivity, and enhancing inhibition was able to ameliorate paw withdrawal signatures of neuropathic pain, like shaking. Collectively, these results suggest that the Gr plays a specific role in mediating hypersensitivity to low-threshold, innocuous mechanical stimuli during neuropathic pain, and that Gr activity contributes to affective, pain-associated phenotypes of mechanical allodynia. Therefore, these brainstem circuits work in tandem with traditional spinal circuits underlying allodynia, resulting in enhanced signaling of tactile stimuli in the brain during neuropathic pain.

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↗

bioRxiv2023

Neuron-dependent tuft cell expansion initiates sinonasal allergic Type 2 inflammation

Withdrawal StatementThe authors have withdrawn this manuscript owing to inaccuracies in the calculation of tuft cell numbers and errors in the selection of immunofluorescence images used to support our claims. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

immunology↗

bioRxiv2023

A Hypothalamic Circuit Underlying the Dynamic Control of Social Homeostasis

Social grouping increases survival in many species, including humans1,2. By contrast, social isolation generates an aversive state (loneliness) that motivates social seeking and heightens social interaction upon reunion3-5. The observed rebound in social interaction triggered by isolation suggests a homeostatic process underlying the control of social drive, similar to that observed for physiological needs such as hunger, thirst or sleep3,6. In this study, we assessed social responses in multiple mouse strains and identified the FVB/NJ line as exquisitely sensitive to social isolation. Using FVB/NJ mice, we uncovered two previously uncharacterized neuronal populations in the hypothalamic preoptic nucleus that are activated during social isolation and social rebound and that orchestrate the behavior display of social need and social satiety, respectively. We identified direct connectivity between these two populations of opposite function and with brain areas associated with social behavior, emotional state, reward, and physiological needs, and showed that animals require touch to assess the presence of others and fulfill their social need, thus revealing a brain-wide neural system underlying social homeostasis. These findings offer mechanistic insight into the nature and function of circuits controlling instinctive social need and for the understanding of healthy and diseased brain states associated with social context.

neuroscience↗

bioRxiv2023

Opposing, spatially-determined epigenetic forces impose restrictions on stochastic olfactory receptor choice

Olfactory receptor (OR) choice represents an example of genetically hardwired stochasticity, where every olfactory neuron expresses one out of [~]2000 OR alleles in a probabilistic, yet stereotypic fashion. Here, we propose that topographic restrictions in OR expression are established in neuronal progenitors by two opposing forces: polygenic transcription and genomic silencing, both of which are influenced by dorsoventral gradients of transcription factors NFIA, B, and X. Polygenic transcription of OR genes may define spatially constrained OR repertoires, among which one OR allele is selected for singular expression later in development. Heterochromatin assembly and genomic compartmentalization of OR alleles also vary across the axes of the olfactory epithelium and may preferentially eliminate ectopically expressed ORs with more dorsal expression destinations from this "privileged" repertoire. Our experiments identify early transcription as a potential "epigenetic" contributor to future developmental patterning and reveal how two spatially responsive probabilistic processes may act in concert to establish deterministic, precise, and reproducible territories of stochastic gene expression.

genomics↗

bioRxiv2022

A critical role for touch neurons in a skin-brain pathway for stress resilience

Social touch can act as a stress buffer, reducing behavioral and physiological responses to stressful scenarios. However, skin-brain touch pathways that promote stress resilience remain unknown. Here, we show that mice with an early life genetic ablation of Mrgprb4-lineage touch neurons display stress vulnerability behaviors in adulthood. Chemogenetic activation of these touch neurons reduced corticosterone levels under mild acute stress conditions. In addition, whole-brain c-Fos activity mapping while chemogenetically turning on these neurons uncovered differential neural activity patterns in brain areas relevant to somatosensation, reward, and affect. To gain mechanistic insight into this skin-brain touch pathway for stress susceptibility, we used multi-circuit neurophysiological recordings across seven brain regions at baseline and after stress in mice that had Mrgprb4-lineage touch neurons ablated in early life. Interestingly, the Mrgprb4-lineage neuron-ablated mice have alterations in local field potential phase directionality and power in the theta frequencies in mesolimbic reward regions, which may underlie our observed stress susceptibility phenotype. Together, these studies revealed that sensory neurons in the skin engage networks across the brain to promote stress resilience.

neuroscience↗

bioRxiv2021

Identification of touch neurons underlying dopaminergic pleasurable touch and sexual receptivity

Pleasurable touch during social behavior is the key to building familial bonds and meaningful connections. One form of social touch occurs during sexual encounters. Although sexual behavior is initiated in part by touch, and touch is ongoing throughout copulation, the identity and role of sensory neurons that transduce sexual touch remain unknown. A population of sensory neurons labeled by the G-protein coupled receptor Mrgprb4 detect stroking touch in mice, however, these neurons have never been implicated in any natural social behaviors. Here, we study the social relevance of Mrgprb4-lineage neurons by genetically engineering mice to allow activation or ablation of this population and reveal that these neurons are required for sexual receptivity and sufficient to induce dopamine release in the brain. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce a conditioned place preference and a striking dorsiflexion resembling the lordotic copulatory posture in females. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding: sexual receptivity is supplanted by aggression and a coincident decline in dopaminergic release in the mesolimbic reward pathway. In addition to sexual behavior, Mrgprb4-lineage neurons are also required for social postures induced by female-to-female back touch. Together, these findings establish that Mrgprb4-lineage neurons are the first neurons of a skin-to-brain circuit encoding the rewarding quality of social touch.

neuroscience↗

bioRxiv2021

Behavioral and nociceptor states of inflammatory painacross timescales in 2D and 3D

Ongoing pain is often driven by direct activation of pain-sensing neurons and neuroimmune mediated sensitization. These heightened states of pain alter physiology, reduce motor function, and alter motivation to engage in normal behaviors. The complexity of the pain state has evaded a comprehensive definition, especially in nonverbal animals. Here in mice, we capture the physiological state of sensitized pain neurons at different time points post-inflammation and used computational tools to automatically map behavioral signatures of evoked and spontaneous displays of pain. First, retrograde labeling coupled with electrophysiology of neurons innervating the site of localized inflammation defined critical time points of pain sensitization. Next, we used high-speed videography combined with supervised and unsupervised machine learning tools and uncovered sensory-evoked defensive coping postures to pain. Using 3D pose analytics inspired by natural language processing, we identify movement sequences that correspond to robust representations of ongoing pain states. Surprisingly, with this analytical framework, we find that a commonly used anti-inflammatory painkiller does not return an animals behavior back to a pre-injury state. Together, these findings reveal the previously unidentified signatures of pain and analgesia at timescales when inflammation induces heightened pain states.

neuroscience↗

bioRxiv2021

Chronic paternal morphine exposure increases sensitivity to morphine-derived antinociception

Parental exposure to drugs of abuse such as opioids can have profound and long-lasting effects on reward processing and drug sensitivity across generations. However, little is known about the impact of long-term paternal exposure to morphine on offspring sensitivity to morphine-derived antinociception during painful experiences. To address this question, we constructed a rat pain scale at millisecond timescales to measure mechanical nociception in a multigenerational morphine exposure paradigm. Surprisingly, while developing the pain scale, we found that von Frey hair filaments (VFHs), the most common stimuli used in pain research, are not painful to rats and morphine did not change the touch-like responses elicited by VFHs. We next deployed this novel pain scale to determine whether chronic morphine exposure in sires impacted pain sensitivity in the next generation. Offspring produced from a cross of morphine-treated sires and drug-naive dams, did not show any baseline changes in sensitivity to mechanical nociception. However, morphine-sired male progeny displayed a higher sensitivity to the antinociceptive properties of morphine, as measured by our pain scale. These findings demonstrate that long-term paternal exposure to morphine increases sensitivity to morphine-derived analgesia in the subsequent generation.

neuroscience↗

bioRxiv2020

A machine-vision approach for automated pain measurement at millisecond timescales

Objective and automatic measurement of pain in mice remains a barrier for discovery in both basic and translational neuroscience. Here we capture rapid paw kinematics during pain behavior in mice with high-speed videography and automated paw tracking with machine and deep learning approaches. Our statistical software platform, PAWS (Pain Assessment at Withdrawal Speeds), uses a univariate projection of paw position over time to automatically quantify fast paw dynamics at the onset of paw withdrawal and also lingering pain-related behaviors such as paw guarding and shaking. Applied to innocuous and noxious stimuli across six inbred mouse strains, a linear discriminant analysis reveals a two-dimensional subspace that separates painful from non-painful stimuli on one axis, and further distinguishes the severity of pain on the second axis. Automated paw tracking combined with PAWS reveals behaviorally-divergent mouse strains that display hypo- and hyper-sensitivity to mechanical stimuli. To demonstrate the efficacy of PAWS for detecting hypersensitivity to noxious stimuli, we chemogenetically activated pain-aversion neurons in the amygdala, which further separated the behavioral representation of pain-related behaviors along a low-dimensional path. Taken together, this automated pain quantification approach should increase the ease and objectivity of collecting rigorous behavioral data, and it is compatible with other neural circuit dissection tools for determining the mouse pain state.

neuroscience↗

bioRxiv2019

Evoked and spontaneous pain assessment during tooth pulp injury

Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the rodent orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. Here we use a dental pulp injury model in the mouse and expose the tooth pulp to the outside environment, a procedure we have previously shown produces pulpal inflammation. We demonstrate here with RNAscope technology in the trigeminal ganglion of injured mice, an upregulation of genes that contribute to the inflammatory pain state. Using both evoked and spontaneous measures of pain in the orofacial area, including application of von Frey Hair filaments and pain feature detection with the mouse grimace scale, we reveal a differential timeline of induction of spontaneous pain versus mechanical allodynia following pulpal injury. This work demonstrates that tooth pain can be easily assessed in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammation and other forms of trigeminal pain.

neuroscience↗

bioRxiv2018

High-Speed Imaging of Paw Withdrawal Reflex to Objectively Assess Pain State in Mice

Rodents are often used for studying chronic pain mechanisms and developing new pain therapeutics, but objectively determining the animals pain state is a major challenge. To improve the precision of using reflexive withdrawal behaviors for interpreting the mouse pain state, we adopted high-speed videography to capture sub-second movement features of mice upon hind paw stimulation. We identified several parameters that are significantly different between behaviors evoked by innocuous and noxious stimuli, and combined them to map the mouse pain state through statistical modeling and machine learning. To test the utility of this approach, we determined the pain state triggered by von Frey hairs (VFHs) and optogenetic activation of two nociceptor populations. Our method reliably assesses the \"pain-like\" probability for each mouse paw withdrawal reflex under all scenarios, highlighting the improved precision of using this high resolution behavior-centered composite methodology to determine the mouse pain state from reflexive withdrawal assays.

neuroscience↗

bioRxiv2017

Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying the pain fovea, we sparsely traced non-peptidergic nociceptors across the body using a newly generated MrgprDCreERT2 mouse line. We found that mouse plantar paw skin also has a low density of MrgprD+ neurites, and individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the magnification of plantar paw regions to contribute to the pain fovea.

neuroscience↗