Biology subjects

Bains, J.

Publications and source records attributed to Bains, J..

6 recordsLinked to original sources

bioRxiv2026

A transient hypothalamic CRH signal coordinates social investigation in mice

Successful navigation of the social environment depends on the ability to rapidly evaluate conspecifics and adjust behaviour accordingly. Encounters with unfamiliar individuals are particularly challenging because they introduce uncertainty about how the interactions may unfold. Such social encounters can lead to beneficial or detrimental outcomes, making rapid assessment critical for survival; yet the neural mechanisms underlying this process remain poorly understood. Corticotropin-releasing hormone synthesizing neurons in the paraventricular nucleus of the hypothalamus (CRHPVN), traditionally viewed as the canonical endocrine controllers of the stress response, have been implicated in processing behaviourally relevant environmental and social information, including the investigation of stressed conspecifics. However, their role in rapidly evaluating conspecifics during social encounters remains unclear. Here, using fibre photometry and optogenetics during ethologically relevant social encounters, we show that CRHPVN neurons exhibit a rapid, transient increase in activity that precedes investigative behaviour. This signal scales with social context, is elevated during exposure to unfamiliar relative to familiar conspecifics, persists across novel environments, and generalizes across unfamiliar strains. In contrast, interactions with juvenile conspecifics and inanimate objects do not elicit this differential activity, indicating that CRHPVN recruitment is not driven solely by novelty. Critically, temporally specific inhibition of CRHPVN neurons during this brief activity window produces lasting changes in behaviour beyond the period of inhibition, including the reduction of appropriate social investigation, indicating that this transient activity is necessary for gating subsequent social behaviour. Together, these findings identify CRHPVN neurons as a rapid integrative node linking hypothalamic function to social evaluation.

neuroscience↗

bioRxiv2025

Hypothalamic recurrent inhibition regulates functional states of stress effector neurons.

Stress triggers rapid and reversible shifts in vital physiological functions from homeostatic operation to emergency response. However, the neural mechanisms regulating such functional stress states remain poorly understood. Here we identify a novel recurrent inhibitory circuit governing functional states of key stress regulatory neurons: corticotropin-releasing hormone (CRH) neurons in the hypothalamic paraventricular nucleus (PVN). Microendoscopic calcium imaging in freely behaving mice revealed synchronized low-activity state at baselines and a reversible high-activity state during mild stress. Ensemble analysis indicated increased dimensionality of network dynamics during high-activity state. Computational modeling of calcium ensemble data, together with independent modeling of single-unit CRHPVN neurons spiking dynamics, converged to show that recurrent inhibition is a key circuit motif for stress-induced functional state transitions. Guided by model predictions, chemogenetic manipulations of PVN-projecting GABAergic neurons (PVN[->]GABA) revealed their roles in constraining CRHPVN neurons to low-activity state at baselines via a prolonged feedback inhibition. Unexpectedly, slow CRHergic excitation was dispensable for driving this prolonged feedback, whereas glutamatergic transmission predominated at CRH[->]PVN[->]GABA excitatory synapses. Incorporating these findings, we refined our computational model to include fast excitation and slow inhibition, yielding new predictions for circuit operation. Together, our results establish recurrent inhibition as a fundamental circuit motif controlling CRHPVN neurons functional states and highlight the value of iterative experiment-model integration in advancing understanding of neural circuits functions.

neuroscience↗

bioRxiv2025

Chemokinesis by a microbial predator

Regulated motility is vital for many cells--both for unicellular microbes and for cells within multicellular bodies. Different conditions require different rates and directions of movement. For the microbial predator Capsaspora owczarzaki, its motility is likely essential for predation. This organism has been shown to prey on diverse organisms, including the schistosome parasites that co-reside with it in Biomphalaria glabrata snails. Capsaspora is also an evolutionary model for the unicellular ancestor of animals. This phylogenic placement makes Capsasporas motility an attractive target for understanding the evolution of motility in animal cells. Until now, little was known of how Capsaspora regulates it rate and direction of motility. Here we found that it exhibits chemokinesis (increased movement in response to chemical factors) in response to proteins released from prey cells. Chemokinesis also occurs in response to pure proteins--including bovine serum albumin. We found that this chemokinesis behavior is dependent on Capsaspora cell density, which suggests that the regulated motility is a cooperative behavior (possibly to improve cooperative feeding). We developed a mathematical model of Capsaspora motility and found that chemokinesis alone does not benefit Capsaspora predation. However, when coupled with chemotaxis (directional motility along a chemical gradient toward prey), chemokinesis may improve predation. Finally, we quantitatively analyzed Capsasporas previously reported chemotaxis behavior. These findings lay a foundation for characterizing the mechanisms of regulated motility in a predator of a human pathogen and a model for the ancestor of animals.

biochemistry↗

bioRxiv2024

Maternal high-fat, high-sucrose diet-induced excess adiposity is linked to placental hypoxia and disruption of fetoplacental immune homeostasis in late gestation

Maternal excess adiposity (i.e., overweight and obesity) at conception is linked to numerous signs of malperfusion and inflammatory injury in the placenta. Previous reports have suggested that obesity-associated placental malperfusion may trigger a state of fetoplacental hypoxia, contributing to adverse health outcomes within and beyond the perinatal period. However, many previous studies have relied on indirect measures of tissue oxygen saturation, including readouts influenced by external inflammatory stressors. Direct comparisons of tissue oxygen saturation at the uteroplacental interface in pregnancies complicated by excess adiposity are lacking. Here, we used a mouse model of chronic preconception high-fat, high-sucrose (HFHS) diet feeding to model the impacts of an obesogenic milieu on placental oxygenation near term gestation (E17.5). We found that both placental junctional and labyrinth zone tissues were relatively hypoxic in HFHS pregnancies compared to chow-fed controls (CON). However, this was not associated with enhanced HIF-1 expression in labyrinth tissues. Similarly, placentas from CON and HFHS dams did not exhibit gross differences in morphology or vessel density and pericyte coverage. However, HFHS placentas have a greater burden of histopathological lesions, including tissue calcification and fibrinoid deposition within the labyrinth zone. Calcified placental tissue coincided with the destruction of vasculosyncytial membranes and macrophage-dense foci, alongside altered expression of immunomodulatory and chemotactic cytokines within the labyrinth zone proteome, which differed in magnitude with fetal sex. While fetal growth was not markedly affected, fetuses from HFHS pregnancies exhibited higher levels of circulating IL-6, prolactin, CXCL1, and CCL2. Collectively, these data confirm that diet-induced maternal excess adiposity leads to a relative state of placental hypoxia, even in the absence of marked growth restriction or fetal demise. While this hypoxic state is not linked to gross morphological abnormalities, it is associated with a greater histopathological burden indicative of local malperfusion and inflammation, and an altered fetal inflammatory and endocrine milieu in late gestation. These findings provide new insight into mechanisms by which an obesogenic environment during pregnancy compromises placental function and contributes to the long-term programming of chronic disease susceptibility.

developmental biology↗

bioRxiv2024

Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling

Excess maternal adiposity (i.e., overweight and obesity) during pregnancy has been linked to impaired uteroplacental perfusion, compromised placental development, and a higher risk of adverse pregnancy outcomes. Owing to the nature of chronic inflammation and immune dysregulation accompanying excess adiposity, disruption of leukocyte-mediated tissue remodelling and immunoregulation within the decidua have emerged as likely drivers contributing to suboptimal placental function in pregnancies impacted by maternal overweight or obesity. However, the impacts of excess adiposity on major populations of innate lymphoid cells (ILCs) and macrophages which orchestrate these processes and the environment that these cells occupy remain vastly understudied. Here, we used a mouse model of chronic high-fat, high-sucrose (HFHS) diet-feeding to characterize the impacts of an obesogenic milieu on decidual immune dynamics during placental development at mid-gestation (E10.5). HFHS pregnancies exhibited marked increases in total decidual leukocyte abundance, driven by population-level increases in tissue-resident and conventional NK cells, and MHC-II+ macrophages. This was not associated with abnormalities in implantation site morphology or decidual spiral artery remodelling but was coincident with histological patterns of local inflammation. In line with this, expression of canonical proinflammatory cytokines and chemokines were moderately upregulated in bulk decidual tissue of HFHS dams. This was accompanied by more potent elevations in multiple mediators of angiogenesis, endothelial activation, and coagulation in HFHS decidual tissue. Collectively, these findings point towards pathological vascular inflammation and possibly dysregulated decidual angiogenesis in the first half of pregnancy as factors predisposing to reduced placental efficiency, malperfusion, and inflammation seen in pregnancies affected by maternal overweight and obesity.

developmental biology↗

bioRxiv2021

Markerless mouse tracking for social experiments

Automated behavior quantification requires accurate tracking of animals. Simultaneous tracking of multiple animals, particularly those lacking visual identifiers, is particularly challenging. Problems of mistaken identities and lost information on key anatomical features are common in existing methods. Here we propose a markerless video-based tool to simultaneously track two socially interacting mice of the same appearance. It incorporates conventional handcrafted tracking and deep learning based techniques, which are trained on a small number of labeled images from a very basic, uncluttered experimental setup. The output consists of body masks and coordinates of the snout and tail-base for each mouse. The method was tested on a series of cross-setup videos recorded under commonly used experimental conditions including bedding in the cage and fiberoptic or headstage implants on the mice. Results obtained without any human intervention showed the effectiveness of the proposed approach, evidenced by a near elimination of identities switches and a 10% improvement in tracking accuracy over a pure deep-learning-based keypoint tracking approach trained on the same data. Finally, we demonstrated an application of this approach in studies of social behaviour of mice, by using it to quantify and compare interactions between pairs of mice in which some are anosmic, i.e. unable to smell. Our results indicated loss of olfaction impaired typical snout-directed social recognition behaviors of mice, while non-snout-directed social behaviours were enhanced. Together, these results suggest that the hybrid approach could be valuable for studying group behaviors in rodents, such as social interactions.

bioengineering↗