Biology subjects

kodandaramaiah, S. B.

Publications and source records attributed to kodandaramaiah, S. B..

7 recordsLinked to original sources

bioRxiv2026

Coordinated Representational Drift Across the Mouse Cortex

Cortical neurons continuously change their spatial tuning properties over days and weeks, yet how this representational drift is coordinated across distributed cortical networks remains unknown. Using a robotic cranial exoskeleton for chronic widefield calcium imaging with cellular resolution, we tracked over 110,000 unique layer 2/3 neurons across retrosplenial, visual, somatosensory, and motor cortices in mice navigating a figure-8 maze spanning 47 days. Single-neuron spatial tuning properties followed a posterior-to-anterior gradient, with retros-plenial and visual cortices containing the highest proportions of spatially tuned neurons. This was dissociated from local functional coupling, which was strongest in somatosensory cortex. Population activity formed a low-dimensional manifold whose geometry mirrored the structure of the maze. Despite these regional differences, all four regions decorrelated with similar exponential timescales, and session-specific deviations from each regions decay trajectory were correlated across all pairwise region combinations, suggesting that drift was coordinated rather than independent across the dorsal cortex. This coordination persisted after controlling for shared behavioral fluctuations. Furthermore, drift was consistent with an orthogonal transformation of the population code that preserved the geometric relationships between spatial representations across sessions despite continuous drift in single-neuron tuning.

neuroscience↗

bioRxiv2026

ML-guided robotic microinjection of single neurons in human brain organoids

Human brain organoids have emerged as powerful models for studying the physiology, pathology, and evolution of the human brain. When combined with single-cell approaches, they offer the potential to directly probe the dynamics and mechanisms underlying cell fate decisions. A major technical bottleneck, however, remains the ability to reliably visualize and manipulate individual cells within their dense and heterogeneous tissue environment. Microinjection has proven effective for this purpose, allowing direct delivery of membrane-impermeable probes into single cells within intact tissue. Despite its versatility, widespread adoption of microinjection has been limited by its technically demanding and low-throughput nature. Automated microinjection systems developed for murine tissue have demonstrated that robotics can overcome these limitations, enabling systematic single-cell lineage tracing at scale. Here, we present a vision-guided robotic system capable of imaging organoid slices, identifying tissue boundaries, and targeting specific single cells for microinjection. This approach is generalizable across murine and human tissues and enables high-throughput single-cell manipulation, opening new avenues for studying human brain development at scale.

bioengineering↗

bioRxiv2026

Cortex-Wide Cellular Imaging in Freely Locomoting Mice Using Cortex Camera Array Microscope (CortexCAM)

Understanding single-cell neuronal activity across multiple brain regions in the context of ethologically relevant behaviors is a major goal in systems neuroscience. We have engineered the Cortex Camera Array Microscope (CortexCAM), integrating four miniaturized fluorescence imaging microscopes to simultaneously capture cellular activity from contiguous fields of view spanning over 48 mm2 of the dorsal cortex. The CortexCAM is capable of imaging > 9000 individual neurons across much of the primary and secondary motor, somatosensory, visual, retrosplenial, and association cortices across both hemispheres of the dorsal cortex. The compact nature of the CortexCAM allows integration into a passive mechanical gantry system to form the mobile CortexCAM. The mobile CortexCAM allows volitional control of the animals translational motion (x, y) and rotational motion (yaw) in physical behavior arenas. We then use the mobile CortexCAM to perform cortex-wide cellular resolution imaging in freely locomoting mice performing alternating choice tasks, as well as during social interactions. Thus the CortexCAM allows studying cortex-wide cellular dynamics in behaviors that cannot be achieved in headfixed settings.

neuroscience↗

bioRxiv2024

Computer vision guided open-source active commutator for neural imaging in freely behaving animals

Recently developed miniaturized neural recording devices that can monitor and perturb neural activity in freely behaving animals have significantly expanded our knowledge neural underpinning of complex behaviors. Most miniaturized neural interfaces require a wired connection for external power and data acquisition systems. The wires are required to be commutated through a slip ring to accommodate for twisting of the wire or tether and alleviate torsional stresses. The increased trend towards long term continuous neural recordings have spurred efforts to realize active commutators that can sense the torsional stress and actively rotation the slip ring to alleviate torsional stresses. Current solutions however require addition of sensing modules. Here we report on an active translating commutator that uses computer vision (CV) algorithms on behavioral imaging videos captured during the experiment to track the animals position and heading direction in real-time and uses this information to control the translation and rotation of a slipring commutator to accommodate for accumulated mouse heading orientation changes and position. The CV guided active commutator has been extensively tested in three separate behavioral contexts and we show reliable cortex-wide imaging in a mouse in an open-field with a miniaturized widefield cortical imaging device. Active commutation resulted in no changes to measured neurophysiological signals. The active commutator is fully open source, can be assembled using readily available off-the-shelf components, and is compatible with a wide variety of miniaturized neurophotonic and neurophysiology devices.

neuroscience↗

bioRxiv2023

Mesoscale Ca2+ imaging reveals networks of Purkinje cell dendritic and somatic modulation, with divergent roles of activity versus correlation during behavior

A major challenge in cerebellar physiology is determining how the stereotypic, conserved circuitry of the cerebellar cortex, with its dominant parasagittal and transverse architectures, underlies its fundamental computations and contributions to behavior. To interrogate Purkinje cell dynamics at this parasagittal and transverse spatial scale, we implemented a novel approach for awake, chronic, wide-field Ca2+ imaging of the cerebellar cortex. We observe two functionally and spatially distinct Purkinje cell networks, reflecting their dendritic and somatic activities, respectively. Both dendritic and somatic networks exhibit bilateral, widespread activation during behavior, but with diverse patterns of spatial correlations occurring primarily along the parasagittal and transverse directions, consistent with the main geometry of the cerebellar cortex. Somatic network correlation dynamics are robustly modulated by prediction errors, and even reflect ultimate behavioral outcomes. These results provide a novel link between cerebellar structure and function, with the correlation dynamics of Purkinje cell activity a key feature.

neuroscience↗

bioRxiv2022

3D morphometric analysis of mouse skulls using microcomputed tomography and computer vision

Morphometric studies have provided crucial insights into the skull anatomy of commonly used wildtype (WT) laboratory mice strains such as the C57BL/6. With the increasing use of transgenic (TG) animals in neuroscience research, it is important to determine whether the results from morphometric studies performed on WT strains can be extended to TG strains derived from these WT strains. We report a new computer vision-based analysis pipeline for surveying mouse skull morphology using microcomputed tomography (CT) scans. We applied this pipeline to study and compare eight cohorts of adult mice from two strains, including both male and female mice at two age points. We found that the overall skull morphology was generally conserved between cohorts, with only 13% of landmark distance differences reaching statistical significance. In addition, we surveyed the dorsal skull bone thickness differences between cohorts. We observed significantly thicker dorsal, parietal, and/or interparietal bones in WT, male, or older mice for 53% of thickness comparisons. This knowledge of dorsal skull bone thickness has potential implications for surgical planning through skull imaging and has applications in automating cranial microsurgeries on mice.

neuroscience↗

bioRxiv2021

Polymer skulls with integrated transparent electrode arrays for cortex-wide opto-electrophysiological recordings

Electrophysiological and optical imaging provide complementary neural sensing capabilities - electrophysiological recordings have the highest temporal resolution, while optical imaging allows recording the activities of genetically defined populations at high spatial resolution. Combining these complementary, yet orthogonal modalities to perform simultaneous large-scale, multimodal sensing of neural activity across multiple brain regions would be very powerful. Here we show that transparent, inkjet-printed electrocorticography (ECoG) electrode arrays can be seamlessly integrated with morphologically conformant transparent polymer skulls for multimodal recordings across the cortex. These eSee-Shells were implanted on transgenic mice expressing the Ca2+ indicator GCaMP6f in cortical excitatory cells and provided a robust opto-electrophysiological interface for over 100 days. eSee-Shells enable simultaneous mesoscale Ca2+ imaging and ECoG acquisition under anesthesia as well as in awake animals presented with sensory stimuli. eSee-Shells further show sufficient clarity and transparency to observe single-cell Ca2+ signals directly below the electrodes and interconnects. Simultaneous multimodal measurement of cortical dynamics reveals changes in both ECoG and Ca2+ signals that depend on the behavioral state.

neuroscience↗