Biology subjects

Vishwanath, A.

Publications and source records attributed to Vishwanath, A..

7 recordsLinked to original sources

bioRxiv2026

L-DOPA Rescues Reach Height but Not Trajectory Area in a Bimanual String-Pulling Behavior in Parkinsonian Rats

While gross motor changes in Parkinson's disease, bradykinesia, hypokinesia, difficulty initiating movement, have been well studied in rodent models of the disease, limb movements, and especially bimanual coordination deficits, are more difficult to study in these animal models. Here we describe a novel bimanual string-pulling task that can be used to generate a rich repertoire of behaviors that require limb and bimanual coordination in rats with unilateral 6-hydroxydopamine (6-OHDA) lesion. We show that 6-OHDA lesion significantly reduces string speed, pulling bout duration, paw speed especially during reaching, and reduces the area of paw trajectories during pulling. However, it does not affect the variability around that movement trajectory. We also show that levodopa (L-DOPA) treatment restores many of these measures but not all. L-DOPA restores paw speed and string-pulling speed and fully restores paw reach height and pulling bout duration, but has no effect on trajectory area. Together, our results demonstrate that dopamine depletion differentially effects features of this bimanual coordination task, that L-DOPA mostly, but not fully, restores string pulling performance, and opens up a new avenue for measuring the effect of Parkinson's disease treatments on motor movement, allowing for better assessment of how effectively treatments restore motor activity.

neuroscience↗

bioRxiv2026

Hippocampus-evoked polysynaptic responses in the medial prefrontal cortex are attenuated in aged rats.

The hippocampus-medial prefrontal cortex (mPFC) circuit is critical for spatial working memory and decision-making. Age-associated changes to these functions are attributed to alterations in this circuit, although the exact mechanisms remain unclear. These regions are connected via monosynaptic projections from the intermediate (iHC) and ventral (vHC) hippocampus to the infralimbic (IL) and prelimbic (PL) regions of the mPFC. We examined the functional connection between these regions in young (10-12 months) and aged (23-26 months) male F344 rats. High-density Neuropixels probes were used to record mPFC field potentials (fEPSPs) and single-unit responses to electrical stimulation of iHC and vHC. We observed that hippocampal stimulation evoked both short-latency (5-35 ms) monosynaptic and long-latency (35-100 ms) polysynaptic responses in PL and IL cortices. Monosynaptic responses, reflecting direct hippocampal-prefrontal synaptic transmission, had lower vHC-evoked IL fEPSP amplitude in aged rats, while other subregional HC-mPFC connections and evoked neural firing were preserved. The polysynaptic responses, reflecting local mPFC circuit recruitment, also had lower IL fEPSP amplitude in aged rats, while evoked neural firing in the polysynaptic window was diminished in both mPFC regions. Age-associated polysynaptic changes in mPFC neural responses differed by the HC stimulation site. In aged rats, iHC stimulation resulted in a lower proportion of recruited neurons, while vHC stimulation resulted in diminished evoked mPFC firing rates, compared to young rats. Our findings demonstrate that aging selectively impairs vHC-mPFC direct synaptic transmission and mPFC local responses, with infralimbic circuits showing particular vulnerability. These circuit-level deficits may contribute to age-related impairments in cognitive flexibility. Significance StatementAging impairs spatial working memory and decision making which require hippocampus-prefrontal communication. We examined the age-related changes in the functional connection of the intermediate (iHC) and ventral (vHC) hippocampus direct projection onto prelimbic (PL) and infralimbic (IL) regions of the mPFC. We found the vHC-evoked IL monosynaptic excitatory field potential amplitude was lower in aged rats, while other HC-mPFC connections were preserved. The evoked polysynaptic excitatory field potentials and single-unit responses were attenuated with age in both mPFC regions with responses differing between HC stimulation sites. These results identify subregional changes in how hippocampal inputs alter mPFC local recruitment in aging that may explain related impairments in cognitive flexibility.

neuroscience↗

bioRxiv2026

Modeling the journey as well as the destination: a control theory account of rotational navigation

Navigation requires estimating heading and transforming these estimates into actions. Prior models explain how self-motion and landmark cues are combined into heading estimates, but less is known about how these estimates are iteratively transformed into motor commands to reach a goal. Here, we hypothesized that navigation operates as a closed-loop process in which ongoing movement is updated by sensory prediction errors. To test this hypothesis, participants performed a goal-directed rotation task in virtual reality. On select trials, visual landmarks were shifted during movement, inducing a prediction error between the heading expected from self-motion estimates and the heading observed from the shifted landmarks. In parallel, we developed a closed-loop model of turning behavior that represents heading and angular velocity as jointly estimated states over time. This model accounts not only for final position--the destination--but also for the movement dynamics that produce it--the journey. The model predicts that landmark-induced visual prediction errors should produce rapid corrective changes in movement. Participant turning behavior qualitatively paralleled these model dynamics: acceleration changed after visual feedback, with larger landmark mismatches producing larger corrective responses. Together, these findings suggest that naturalistic movement depends on continuously transforming heading estimates into motor command through closed-loop control.

neuroscience↗

bioRxiv2026

Illusory path configurations reveal age-related differences in egocentric pointing variability

A consistent finding across studies with older adults is that they typically perform worse at spatial memory tasks, particularly those conducted in virtual reality and involving novel environments, compared to young adults. While the underlying reasons for this difference remain unclear, some proposed hypotheses include differences in sensory cue integration and cue conflict resolution. Here, we tested older (n = 29) and young adults (n = 28) in immersive and walkable virtual reality using both correctly rendered and illusory hallways to test how visual cues (i.e., an intersection) and self-motion cues are integrated. In the illusory or false-intersection condition, we hypothesized that participants who walked an uncrossed path would merge two disconnected intersections, creating the illusion of a crossed path. The overall accuracy and pointing patterns were similar between young and older adults in both true- and false-intersection conditions. We did find, however, a significant age by condition interaction effect in egocentric pointing variability where older adults showed lower variability in the illusory condition and higher variability in the control condition. At the same time, older adults also drew worse maps for the control condition compared to young adults. However, the pointing error correlated with the accuracy of maps drawn regardless of age, suggesting that the pointing patterns shown by both age groups related to their underlying representations of the paths. Our findings are inconsistent with a global deficit in allocentric navigation or path integration and instead suggest that more subtle differences in strategy use might manifest with age.

neuroscience↗

bioRxiv2025

Opposing responses of hippocampal theta oscillations to running and a forelimb-dominated sensorimotor behavior

Hippocampal theta oscillations regulate the timing of neurons to support navigation, memory formation, and sensorimotor integration. Theta is modulated by running speed, breathing, whisking, and jumping and increases in tasks involving memory encoding or retrieval. The positive relationship between theta frequency and running speed is believed stabilize hippocampal representations of space amid movement variability. Here, we incorporated a novel string-pulling task to determine if established relationships between movement and theta hold when progress to a reward is determined by the length of string pulled. This task eliminates many speed-associated inputs, such vestibular, visual, and hindlimb information, and allows an unprecedented level of precision in the analysis of individual paw movements. Given that animals move the string a fixed length to acquire a reward, we predicted that the positive relationship between theta frequency and speed would hold. ApproachFive Sprague Dawley rats (4 mo.) were trained to continuously pull a string a fixed distance of 208 cm using an automated string-pulling system and run on a track for food reward. Local-field data was acquired from electrodes in dorsal CA1. ResultsRelationships between theta and movement speed were distinct during string pulling and running. While theta was robust in both conditions, frequency was significantly reduced during string-pulling and showed no speed-frequency coupling, unlike running. This difference could result from the conflict between hindlimb and forelimb signals, with only forelimb movement signaling advancement. Fine-grained analysis of paw movements during string-pulling (lift, advance, grasp, pull, push) revealed that theta power and frequency peaked during the contralateral paws downward push despite paw speed being low during this action. This suggests that theta frequency and power could respond to effort rather than purely kinematic information. Notably, running-associated theta may similarly reflect both speed and effort as most locomotor tasks conflate these variables. Finally, theta phase aligned from one reach-pull cycle to the next during the downward pull motion - the first action that directly advances the string forward. Since phase-locking has been associated with sensorimotor gating, synchrony at this point could reflect the gating of inputs that are the most causally relevant for reaching the reward, potentially facilitating integration of action-outcome signals for memory encoding and navigation. Taken together, these data support a dual-scale view of hippocampal processing and theta-band activity where macroscale theta activity requires suprathreshold sensory, vestibular, and proprioceptive drive and microscale theta remains sensitive to subsecond limb movements.

neuroscience↗

bioRxiv2023

Automated system for training and assessing string-pulling behaviors in rodents

String-pulling tasks have been used for centuries to study coordinated bimanual motor behavior and problem solving. String pulling is rapidly learned, ethologically grounded, and has been applied to many species and disease conditions. Typically, training of string-pulling behaviors is achieved through manual shaping and baiting. Furthermore, behavioral assessment of reaching, grasping, and pulling is often performed through labor intensive manual video scoring. No system, to our knowledge, currently exists for the automated shaping and assessment of string-pulling behaviors. Here we describe the PANDA system (Pulling And Neural Data Analysis), an inexpensive hardware and software system that utilizes a continuous string loop connected to a rotary encoder, feeder, microcontroller, high-speed camera, and analysis software for assessment and training of string-pulling behaviors and synchronization with neural recording data. We demonstrate this system in unimplanted rats and rats implanted with electrodes in motor cortex and hippocampus and show how the PANDA system can be used to assess relationships between paw movements and single-unit and local-field activity. We also found that automating the shaping procedure significantly improved overall performance, with rats regularly pulling >100 meters during a 15-minute session. In conclusion, the PANDA system will be of general use to researchers investigating motor control, motivation, and motor disorders such as Parkinsons disease, Huntingtons disease, and stroke. It will also support the investigation of neural mechanisms involved in sensorimotor integration. HighlightsO_LIHigh-speed tracking of continuous grasping and pulling behaviors. C_LIO_LIAutomated and adaptive reinforcement of string-pulling behavior. C_LIO_LIIntegration with neural recording and video tracking systems. C_LIO_LIOpen-source software and hardware. C_LI Supplemental FilesThe supplemental pdf contains additional designs and behavioral data and has been uploaded. Source code and 3D and laser cut design files can be found at: https://github.com/CowenLab/String_Pulling_System/ Videos are in the GitHub repository at: https://github.com/CowenLab/String_Pulling_System/tree/main/Videos

bioengineering↗

bioRxiv2022

Challenges in Improving Genomic Literacy: Results from National and Regional Surveys of Genomic Knowledge, Attitudes, Concerns, and Behaviors

PurposeInformation about genomics is increasingly available to mainstream society, with more and more emphasis on using genomic information to make health care decisions. To determine how prepared people are to use this knowledge to make critical health-related decisions, we assessed the publics level of genomic literacy and whether this knowledge affects their engagement in behaviors related to genomics, such as getting genetic testing. MethodsA survey assessing perceived and actual knowledge, attitudes, concerns, sources of information, and behaviors related to genomics was administered to national and regional samples of participants. A hierarchical linear regression tested whether knowledge and attitudes predicted engagement in behaviors related to genomics. ResultsParticipants had good basic knowledge of genetics, though they were less familiar with the term "the human genome." They also displayed positive attitudes towards genomic research, despite expressing many concerns. Both greater knowledge and more positive attitudes significantly and independently predicted greater engagement in genetic testing and other related proactive health behaviors. ConclusionKnowledge and concerns about genomics impact the publics ability and willingness to obtain genetic testing and engage in other proactive health behaviors. The publics genomic literacy could be enhanced by integrating their knowledge (e.g of DNA) with broader concepts (e.g. the human genome and genomics) and how they relate to health. Future research is needed on interventions that do this, to improve the publics genomic literacy through relationships that build trust

scientific communication and education↗