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Vidva, R.

Publications and source records attributed to Vidva, R..

3 recordsLinked to original sources

Intrinsic Gestational Timing Governs Human Cerebellar Development After Preterm Birth

Intrinsic programs shape brain maturation, yet which are perturbed by prematurity, and the molecular pathways involved remain unknown. The human cerebellum serves as a paradigm of extrauterine development; its accelerated growth and circuit formation align with the third trimester, a period disrupted by preterm delivery. Through multimodal datasets encompassing in vivo neuroimaging and neurodevelopmental outcomes with postmortem spatial-transcriptomic and histopathological profiling, we show that prematurity diverts the cerebellar developmental trajectory. Cerebellar growth and functional outcomes scaled with gestational age, despite modifying perinatal exposures. Spatially resolved developmental programs underlying macroscopic trajectories were marked by incomplete granule cell maturation and impaired Purkinje cell structural refinement, indicating lineage-specific developmental asynchrony. Thus, prematurity constitutes biologically displaced maturation, in which infants of equivalent post-menstrual age occupy divergent developmental states.

neuroscience↗

Prematurity Reprograms Cerebellar Development and Long-Term Behavior

Preterm survivors often develop motor and socio-cognitive impairments that implicate altered cerebellar development, yet the underlying mechanisms remain poorly understood. A key challenge is that prematurity involves overlapping perinatal insults that converge on the developing brain, making their individual effects difficult to disentangle. Here, we model two major prematurity-associated insults, maternal immune activation (MIA) and neonatal hypoxia (Hx), in mice. By controlling timing and sequence, we define how these insults shape cerebellar assembly during rapid maturation. Comparative analysis with human tissue confirmed that these insults recapitulate key features of the human preterm cerebellum, establishing the translational validity of this model for dissecting insult-specific outcomes. Behavioral and kinematic profiling revealed divergent motor and social phenotypes, which we traced to insult-specific cerebellar remodelling. Hypoxia compromised both granule cell maturation in the internal granule layer and the principal excitatory afferents to Purkinje cells, a circuit state that manifested as impaired motor execution and stereotyped, sensory-disengaged social investigation. Maternal immune activation, by contrast, expanded the granule cell progenitor layer and reduced Purkinje cell dendritic complexity, a phenotype that preserved social preference but reorganized the kinematic structure of social investigation. When hypoxia followed maternal immune activation, it acted on this primed substrate to produce a distinct state in which the features established by prior inflammation were compounded by granule cell proliferative arrest, progressive mitochondrial dysfunction, and aberrant, hyper-interactive social investigation. Together, these findings reframe prematurity-associated insults as cerebellar reprogramming events shaped by both the identity and sequence of insults, linking distinct mechanistic substrates to divergent neurodevelopmental outcomes.

neuroscience↗

MyVivarium: A cloud-based lab animal colony management application with near-realtime ambient sensing

Management of research-animal colonies is vital for lab productivity in preclinical research. Labs often rely on inefficient paper-based or spreadsheet-based methods to manage animal colonies. Dedicated software-based solutions are generally expensive and many lack remote access. Currently available open-source alternatives are difficult to implement and deploy. These solutions also do not have the capability to track ambient variables that affect colony well-being. We built MyVivarium, an open-source database management web application to address these gaps. MyVivarium can be easily deployed to the cloud and sustained for a cost comparable to starting and maintaining a lab website. Using MyVivarium, lab members can collaboratively track individual animals within a database. Physical identities of cages map onto the database using QR codes, enabling quick and easy record-keeping on mobile devices. Lab administrators can assign tasks to users with reminders for experiments or cage maintenance. Finally, we designed a low-cost system to sense ambient humidity, temperature, vivarium worker activity, and room illuminance. These data are then sent to MyVivarium in realtime providing information relevant to colony well-being. Taken together, MyVivarium is a novel, open-source, cloud-based application template that provides a low-cost, simple, and efficient way to digitally manage research-animal colonies.

bioinformatics↗