Biology subjects

Sathyanesan, A.

Publications and source records attributed to Sathyanesan, A..

5 recordsLinked to original sources

bioRxiv2026

An integrated stereotaxic injection architecture for mouse intracranial surgeries with AI-driven domain expertise

Stereotaxic intracranial microinjection in mice is a critical step in neuroscience workflows, enabled by robust hardware design, precise operation, and neuroanatomical expertise. Manual injections are prone to error and stereotax-mountable commercial automated injectors are extremely expensive. Further, the knowledge needed for performing accurate intracranial injections and surgeries is heterogeneous and disparate. Here we demonstrate the design and characterization of the UD Neuroinjector software-hardware-knowledge architecture, which serves to both reduce the cost of performing precisely controlled stereotaxic microinjections and provide a web platform for planning accurate targeting of specific mouse brain regions. We designed the UD Neuroinjector using low-cost hardware and 3D-printed parts, with a total build-cost of $300 --- less than 0.1x the cost of a commercial injector. Arduino-based firmware enables programmable flow rates, automated injection and extraction, and manual joystick control. Capillary-fluid measurements show stable, highly linear displacement (R2 > 0.93) at commonly used injection rates. In a head-to-head comparison with a commercial injector, in vivo DAPI injections into the mouse thalamus showed comparable spread and DAPI+ cell counts. For effective experimental design of intracranial injections, the web-based components of our architecture provide AI-enabled assistance and atlas-guided navigation. We used a hybrid retrieval-augmented generation (RAG) approach to ground AI-assisted protocol guidance for mouse intracranial surgeries using a corpus of 3,738 papers. Using the Common Coordinate Framework version 3 (CCFv3), we designed an interactive tool for identifying target coordinates. Together, the UD Neuroinjector architecture integrates and enables efficient knowledge discovery, experimental design, planning, and implementation of mouse intracranial surgeries.

neuroscience↗

bioRxiv2025

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↗

bioRxiv2025

Behavior decoding delineates seizure microfeatures and associated sudden death risks in mice

Behavior and motor manifestations are distinctive yet often overlooked features of epileptic seizures. Seizures can result in transient disruptions in motor control, often organized into specific behavioral patterns that can inform seizure types, onset zones, and outcomes. However, refined analysis of behaviors in epilepsy remains challenging in both clinical and preclinical settings. Current manual video inspection approaches are subjective, time-consuming, and often focus on gross and ambiguous descriptions of seizure behaviors, overlooking much of the intricate behavioral dynamics and action kinematics. Here, we utilized two machine learning-aided tools, DeepLabCut (DLC) and Behavior Segmentation of Open Field in DLC (B-SOiD), to decode previously underexplored behavior and action domains of epilepsy. We identified 63 interpretable behavior groups during seizures in a population of 32 genetically diverse mouse strains. Analysis of these behavior groups demonstrates significant differential behavior expression and complexity that can delineate distinct seizure states, unravel intrinsic seizure progression over time, and inform mouse strain backgrounds and genotypes. We also identified seizure behavior patterns and action/subaction kinematics that determine the risks of sudden unexpected death in epilepsy (SUDEP). These findings underscore the significant potential for translation into inpatient settings for video analysis in epilepsy monitoring units and outpatient settings via home surveillance devices and smartphones. One Sentence SummaryAI-aided behavior decoding delineates intricate seizure microfeatures in mice.

neuroscience↗

bioRxiv2024

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↗

bioRxiv2019

Placental neurosteroids shape cerebellar development and social behaviour

Compromised placental function or premature loss has been linked to diverse neurodevelopmental disorders 1,2. The placenta is the first functional foetal endocrine organ, but the direct impact of placental hormone loss on foetal brain in late gestation has not been empirically tested. Allopregnanolone (ALLO) is a non-glucocorticoid, progesterone derivative that acts as a positive modulator of GABA-A receptor activity3 with the potential to alter critical GABA-mediated developmental processes 4,5. To directly test the role of placental ALLO, we generated a novel mouse model in which the gene encoding the synthetic enzyme for ALLO (Akr1c14) is specifically deleted in trophoblasts using a tissue-specific Cre-Lox strategy. ALLO concentrations are significantly decreased in late gestation in placenta and brain when placental Akr1c14 is removed, indicating placenta as the primary gestational ALLO source. We now demonstrate that targeted placental ALLO loss leads to permanent changes in brain development in a sex- and regionally-specific manner. Placental ALLO insufficiency led to male-specific cerebellar white matter (WM) abnormalities characterized by excess myelination with increased myelin protein expression, similar to changes reported in boys with autism spectrum disorders (ASD)6,7. Behavioural testing of these mice revealed increased repetitive behaviour and sociability deficits, two hallmarks of ASD, only in male offspring with placental ALLO insufficiency. Notably, a strong positive correlation was seen between the cerebellar contents of myelin basic protein (MBP) and the severity of ASD-like behaviours. A single injection of ALLO during gestation was sufficient to rescue both cerebellar MBP levels and aberrant behaviours. This study reveals a new role for a placental hormone in shaping specific brain structures and behaviours, and suggests that identifying placental hormone insufficiency or preterm loss may offer novel therapeutic opportunities to prevent later neurobehavioural disorders.

neuroscience↗