Biology subjects

Madhav, M. S.

Publications and source records attributed to Madhav, M. S..

8 recordsLinked to original sources

bioRxiv2025

Synchronized path-integration recalibration but distinct landmark-control dynamics in head direction and CA1 place cells

Accurate spatial navigation relies on path integration, a process of tracking ones location by integrating self-motion cues. Path integration uses a gain factor relating self-motion signals to displacement on the cognitive map. This gain is plastic, recalibrating rapidly to match perceived displacements relative to external cues. To elucidate the mechanism of recalibration, we simultaneously recorded from place cells, which instantiate the cognitive map, and head direction (HD) cells, thought to orient the map. Persistent conflict between self-motion and visual feedback induced functionally identical recalibration of path-integration gain in the two neural populations during forward locomotion; however, during locomotor immobility accompanied by head-scanning, HD cells did not exhibit recalibration. Moreover, the two populations manifested differential field-shifting dynamics relative to landmarks during recalibration. These results uncover a tightly coordinated yet behavior-dependent recalibration process across the navigation circuit that achieves a robust yet flexible coupling of the internal sense of position and direction.

neuroscience↗

bioRxiv2025

The Omniroute maze: a novel rodent navigation apparatus that integrates dynamically configurable routes, sensory cues and automated reward delivery

We developed the Omniroute maze, a novel apparatus that enables near-fully automated, high-throughput behavioral experiments in freely moving rodents, combining the experimental control of virtual reality (VR) platforms with the ethological validity of real-world navigation. The maze features movable wall segments that can be programmatically configured to create unique routes within a 90 x 90 cm platform. Four projectors arrayed around the maze perimeter can display distinct visual cues on both sides of any subset of raised gate wall panels and the maze floor as well as play directional auditory cues. A motorized gantry delivers food-based rewards anywhere in the maze. Real-time 3D tracking of the rat and the reward gantry enables closed-loop control of maze topology, cue configuration, and reward delivery. All subsystems are controlled using the Robot Operating System (ROS) framework via a custom Python-based user interface. The Omniroute can reproduce classic behavioral mazes and a variety of novel configurations to test hypotheses on the interactions between routes, cues, and behavior. Automated configuration, tracking, and reward delivery enable high-throughput experiments on complex navigation behaviors without the potential biases introduced by direct experimenter intervention. Designed from the ground up for robust operation, the Omniroute system utilizes affordable hardware and software to facilitate easy fabrication and assembly as well as replicability by other researchers. Significance StatementThe Omniroute system enables high-throughput, automated rodent 2D navigation experiments with real-time control over routes, cues, and reward delivery, comparable to that afforded by modern virtual reality-based systems. In addition, however, the Omniroute supports uninterrupted movement-related behavior, which is critical for assessing the ongoing influence of self-motion cues, while still minimizing confounds from experimenter handling. Naturalistic food-based reinforcement at any location allows for closed-loop behavioral conditioning under diverse task structures. The Omniroute system is one of very few platforms that support near-complete control of available paths, dynamic visual and auditory cues, and naturalistic food-based reinforcement with minimal direct experimenter intervention.

animal behavior and cognition↗

bioRxiv2024

A modular gate system for autonomous control of rodent behavior

Rodent mazes have been used for decades to study the neural basis of behavior. Advancements in rapid prototyping techniques and access to affordable electronics allows laboratories with sufficient expertise in engineering and programming to customize and construct maze apparatuses and behavioral tasks, thereby increasing the ability of their studies to answer specific scientific questions. We designed and built a rodent gate system that lowers this bar of expertise even further. The NC4gate system is a robust mechanical design that can be built using low-cost hardware and execute thousands of cycles before maintenance. Up to 512 gates can be controlled using a single computer. Users can control the gates interactively using a Python-based graphical interface and programmatically using an extensible API. We hope that the open-source hardware / software and extensive documentation enables laboratories to build these affordable and robust gates and seamlessly incorporate automatic behavior control into their existing or new rodent tasks. Significance StatementRodent mazes are used by thousands of laboratories and research institutions across the world to study learning and memory, as well as the effects of pharmacological, genetic and environmental manipulations. Ideally, maze and task designs should be customized to the scientific questions at hand. It is challenging, however, for many laboratories to build, program, and operate custom mazes, requiring them instead to rely on expensive and proprietary commercial solutions. The most complex components of most mazes are moving gates that restrict and direct rodent behavior. Here we provide the open-source hardware and software for a gate system that is extensible, affordable and robust, removing this critical barrier to customized mazes.

animal behavior and cognition↗

bioRxiv2022

Closed-loop control and recalibration of place cells by optic flow

Understanding the interplay between sensory input, endogenous neural dynamics, and behavioral output is key toward understanding the principles of neural computation. Hippocampal place cells are an ideal system to investigate this closed-loop interaction, as they are influenced by both self-motion (idiothetic) signals and by external sensory landmarks as an animal navigates its environment1-9. To continuously update a position signal on an internal "cognitive map", the hippocampal system integrates self-motion signals over time10,11. In the absence of stable, external landmarks, however, these spatial correlates of neuronal activity can quickly accumulate error and cause the internal representation of position or direction to drift relative to the external environment1,5. We have previously demonstrated that, in addition to their known roles in preventing and/or correcting path-integration error, external landmarks can be used as a putative teaching signal to recalibrate the gain of the path integration system6. However, it remains unclear whether idiothetic cues, such as optic flow, exert sufficient influence on the cognitive map to enable recalibration of path integration, or if instead an unambiguous allocentric frame of reference, anchored by polarizing landmark information, is essential for path integration recalibration. Here, we use principles of control theory12,13 to demonstrate systematic control of place fields by pure optic flow information in freely moving animals by using a neurally closed-loop virtual reality system that adjusts optic flow speed as a function of real-time decoding of the hippocampal spatial map. Using this "cognitive clamp", we show that we can not only bring the updating of the map under control of the optic flow cues but we can also elicit recalibration of path integration. This finding demonstrates that the brain continuously rebalances the influence of conflicting idiothetic cues to fine-tune the neural dynamics of path integration, and that this recalibration process does not require a top-down, unambiguous position signal from landmarks.

neuroscience↗

bioRxiv2021

Wide-Angle, Monocular Head Tracking using Passive Markers

Camera images can encode large amounts of visual information of an animal and its environment, enabling high fidelity 3D reconstruction of the animal and its environment using computer vision methods. Most systems, both markerless (e.g. deep learning based) and marker-based, require multiple cameras to track features across multiple points of view to enable such 3D reconstruction. However, such systems can be expensive and are challenging to set up in small animal research apparatuses. We present an open-source, marker-based system for tracking the head of a rodent for behavioral research that requires only a single camera with a potentially wide field of view. The system features a lightweight visual target and computer vision algorithms that together enable high-accuracy tracking of the six-degree-of-freedom position and orientation of the animals head. The system, which only requires a single camera positioned above the behavioral arena, robustly reconstructs the pose over a wide range of head angles (360{whitebullet} in yaw, and approximately {+/-}120{whitebullet} in roll and pitch). Experiments with live animals demonstrate that the system can reliably identify rat head position and orientation. Evaluations using a commercial optical tracker device show that the system achieves accuracy that rivals commercial multi-camera systems. Our solution significantly improves upon existing monocular marker-based tracking methods, both in accuracy and in allowable range of motion. The proposed system enables the study of complex behaviors by providing robust, fine-scale measurements of rodent head motions in a wide range of orientations.

neuroscience↗

bioRxiv2020

Ribosomal Protein Large subunit RPL6 modulates salt tolerance in rice

The extra-ribosomal functions of ribosomal proteins RPL6 and RPL23a in stress-responsiveness have emanated from our previous studies on activation tagged mutants of rice screened for water-use efficiency (Moin et al., 2016a). In the present study, we functionally validated the RPL6, a Ribosomal Protein Large subunit member for salt stress tolerance in rice. The overexpression of RPL6 resulted in tolerance to moderate (150 mM) to high (200 mM) levels of salt (NaCl) in rice. The transgenic rice plants expressing RPL6 constitutively showed better phenotypic and physiological responses with high quantum efficiency, accumulation of more chlorophyll and proline contents, and an overall increase in seed yield compared with the wild type in salt stress treatments. An iTRAQ-based comparative proteomic analysis revealed the high expression of about 333 proteins among the 4,378 DEPs in a selected overexpression line of RPL6 treated with 200 mM of NaCl. The functional analysis showed that these highly expressed proteins (HEPs) are involved in photosynthesis, ribosome and chloroplast biogenesis, ion transportation, transcription and translation regulation, phytohormone and secondary metabolite signal transduction. An in silico network analysis of HEPs predicted that RPL6 binds with translation-related proteins and helicases, which coordinately affects the activities of a comprehensive signaling network, thereby inducing tolerance and promoting growth and yield in response to salt stress. Our overall findings identified a novel candidate, RPL6 whose characterization contributed to the existing knowledge on the complexity of salt tolerance mechanism in plants.

plant biology↗

bioRxiv2020

Target of Rapamycin: function in abiotic stress tolerance in Arabidopsis and its involvement in a possible cross-talk with ribosomal proteins

The Target of Rapamycin (TOR) protein kinase reprograms cellular metabolism under various environmental stresses. The overexpression of TOR in Arabidopsis resulted in increased plant growth including yield and biomass when compared with the wild type under both controlled and limited water conditions. In the present investigation, we report that Arabidopsis plants overexpressing TOR exhibited enhanced tolerance to the osmotic and salt stress treatments. Further to determine the role of TOR in abiotic stresses other than water limiting conditions, which were observed earlier in rice, we have treated high and medium TOR expressing Arabidopsis plants, ATR-1.4.27 and ATR-3.7.32 respectively, with stress-inducing chemical agents such as Mannitol (100 mM), NaCl (150 mM), Sorbitol (200 mM) and PEG (7%). Both the lines, ATR-1.4.27 and ATR-3.7.32 exhibited enhanced tolerance to these stresses. These lines also had increased proline and total chlorophyll contents under stress conditions compared with their corresponding WT counterparts. The upregulation of several osmotic stress inducible genes in Arabidopsis transgenic lines indicated the role of TOR in modulating multi-stress tolerance. In the present investigation, we have also analyzed the transcriptional upregulation of ribosomal protein large and small subunit (RPL and RPS) genes in AtTOR overexpressing rice transgenic lines, TR-2.24 and TR-15.1 generated earlier (Bakshi et al., 2017a), which indicated that TOR also positively regulates the transcription of ribosomal proteins (RP) along with the synthesis of rRNAs. Also, the observations from phosphoproteomic analysis in SALK lines of various Arabidopsis T-DNA insertion mutants of ribosomal proteins showed differential regulation in phosphorylation of p70kDa ribosomal protein S6K1 and comparative analysis of phosphorylation sites for RSK (Ribosomal S6 Kinases) in RPL6, RPL18, RPL23, RPL24 and RPS28C proteins of Arabidopsis, Interestingly, rice showed similarity in their peptide sequences and Ser/Thr positions. These results suggest that the phosphorylation of S6K1 is controlled by loss/ inhibition of ribosomal protein function to switch on/ off the translational regulation for balanced growth and the pathways of both RPs and TOR are interlinked in a cyclic manner via phosphorylation of S6K1 as a modulatory step.

plant biology↗

bioRxiv2018

Recalibration of path integration in hippocampal place cells

Hippocampal place cells are spatially tuned neurons that serve as elements of a \"cognitive map\" in the mammalian brain1. To detect the animals location, place cells are thought to rely upon two interacting mechanisms: sensing the animals position relative to familiar landmarks2,3 and measuring the distance and direction that the animal has travelled from previously occupied locations4-7. The latter mechanism, known as path integration, requires a finely tuned gain factor that relates the animals self-movement to the updating of position on the internal cognitive map, with external landmarks necessary to correct positional error that eventually accumulates8,9. Path-integration-based models of hippocampal place cells and entorhinal grid cells treat the path integration gain as a constant9-14, but behavioral evidence in humans suggests that the gain is modifiable15. Here we show physiological evidence from hippocampal place cells that the path integration gain is indeed a highly plastic variable that can be altered by persistent conflict between self-motion cues and feedback from external landmarks. In a novel, augmented reality system, visual landmarks were moved in proportion to the animals movement on a circular track, creating continuous conflict with path integration. Sustained exposure to this cue conflict resulted in predictable and prolonged recalibration of the path integration gain, as estimated from the place cells after the landmarks were extinguished. We propose that this rapid plasticity keeps the positional update in register with the animals movement in the external world over behavioral timescales (mean 50 laps over 35 minutes). These results also demonstrate that visual landmarks not only provide a signal to correct cumulative error in the path integration system, as has been previously shown4,8,16-19, but also rapidly fine-tune the integration computation itself.

neuroscience↗