Poon, Z. | bioRxiv Science

bioRxiv2026

Early life adversity enhances prosocial helping towards a cagemate and reshapes brain-wide neural activity and network organization

Early life adversity (ELA) is linked to changes in social behavior and emotional regulation and to increased risk for developing mood and conduct disorders. However, the effects of ELA on empathy and its associated behaviors, including prosocial helping, remain poorly understood. Animal models of ELA provide a tractable way to study how early rearing conditions impact prosocial behavior and underlying neural circuitry. In the current study, adult male and female rats reared under maternal separation (MS) or control conditions were tested in a helping behavior task in which they could release a trapped cagemate. Behavior was assessed across repeated testing sessions and brain-wide neural activity was quantified using c-Fos on the final test day. Contrary to our hypothesis, we found that MS-reared rats showed more consistent helping behavior, with shorter latencies to help on average, compared to control-reared animals. In addition, MS-reared rats displayed increased social play following release. At the neural level, MS-reared rats displayed more c-Fos expression across multiple brain regions, including prefrontal, amygdala, sensory, and striatal regions involved in motivation and social decision making. Network analyses further revealed altered functional connectivity in ELA-reared animals, with heightened connectivity in stress-related regions such as the lateral habenula. Together, these findings demonstrate that ELA impacts prosocial helping behavior and is associated with widespread changes in neural activity and network organization. This work provides insight into how early adversity shapes social motivation and the neural systems supporting prosocial behaviors.

neuroscience↗

bioRxiv2022

Topological defects govern mesenchymal condensations, offering a morphology-based tool to predict cartilage differentiation

A critical initial stage of skeletal morphogenesis involves formation of highly compact aggregates of mesenchymal cells, known as mesenchymal condensations, appearing as regularly-spaced pattern of spots. Conventional computational models to understand their patterning have been based on chemotaxis, haptotaxis, and reaction-diffusion equations. In this work, we investigate the mesenchymal condensations from a different perspective, namely topological defects within liquid crystal-like pattern. Using bone marrow-derived mesenchymal stromal cells (bm-MSCs), we observed emergence of cellular swirls in confluent in-vitro cultures, followed by appearance of mesenchymal condensations at the centers of the selfassembled swirls. Specifically, the condensations appeared at the comet-like (+1/2) and spiral-shaped (+1) topological defect sites within the swirl pattern. Next, with the rationale that cellular swirls precede skeletal morphogenesis, and supported with the qualitative observation that swirl pattern-features are donor-specific, we probed the correlation between swirl pattern and the chondrogenic differentiation outcome of bm-MSCs. Towards this, we first generated and imaged cellular swirls systematically across 5 donors by controlling seeding density, culture vessel geometry, and culture duration. We observed that the swirl pattern features quantified as variance of coherency correlated strongly with the cartilage matrix proteins, sulfated glycosaminoglycan and collagen-II, quantified from the standard in-vitro chondrogenic differentiation assay. Our work shows that swirl-pattern quantification provides a novel and powerful tool to predict efficacy of bm-MSCs for in-vitro cartilage regeneration. Significance StatementMesenchymal condensation is a critical stage in the formation of bone and cartilage, where the mesenchymal cells form high density cell clusters that are regularly spaced. In this work, we inspect the patterning of these condensations in-vitro from a novel perspective. We first show that at high density, bone-marrow-derived mesenchymal stromal cells (bm-MSCs) self-assemble to form cellular swirls resembling the vortices in a turbulent flow. This is followed by cell aggregations at the centers of the vortices, which show correspondence to mesenchymal condensations. Interestingly, we observed that the swirl pattern made by bm-MSCs isolated from human donors, varies from individual to individual and correlates with their propensity to differentiate into cartilage. This suggests that swirl pattern quantification via image analysis can be used to predict differentiation outcome, in context of regenerative cell therapy.

biophysics↗