Biology subjects

Mysore, S.

Publications and source records attributed to Mysore, S..

4 recordsLinked to original sources

bioRxiv2026

Modulation of exploration-avoidance behaviors by vmPFC-projecting BLA neurons

The ventromedial prefrontal cortex (vmPFC) is known to regulate exploration-avoidance behaviors. Separately, the basolateral amygdala (BLA), which plays a pivotal role in interpreting the emotional valence of external stimuli, is known to send information about aversive cues to the mPFC. Here, we investigated the role of vmPFC-projecting BLA neurons in modulating exploration-avoidance behaviors. We selectively and reversibly inhibited this subset of BLA neurons using a projection-defined chemogenetic approach in mice engaged in a classic unconditioned exploration-avoidance task, the elevated zero maze (EZM). Saline injection served as a control for administration of the chemogenetic ligand CNO. We found that inhibiting vmPFC-projecting BLA neurons with CNO injections promotes avoidance behaviors. This effect could not be attributed to the effects of injection. It could also not be attributed to repeated maze exposure because, whereas we observed behavioral habituation in naive mice following repeated exposure at 1 hr, in mice mimicking treatment manipulation (IP injection), no habituation was observed at this timepoint. Together, our results reveal that vmPFC-projecting BLA neurons promote safety rather than aversive signals in the context of unconditioned exploration-avoidance behavior. Surprisingly, these findings are directly opposed to previous work that suppressed BLA projection fibers in the mPFC. These contrasting results suggest pathway-dependent roles of mPFC-projecting BLA neurons (direct axonal vs. complex somatic, due to direct + indirect), or alternatively, specializations in the roles of mPFC subregions (vmPFC vs. dmPFC) in exploration-avoidance behavior. Our results also provide guidance for future experimental designs involving repeated exposure to the EZM.

neuroscience↗

bioRxiv2024

Robust characterization of selectivity of individual neurons to distinct task-relevant behavioral states using calcium imaging

Investigations into the neural basis of behavior have recently employed fluorescence imaging of calcium dynamics in a variety of brain areas to measure neural responses. However, across studies, diverse and seemingly subjective methodological choices have been made in assessing the selectivity of individual neurons to task-relevant behavioral states. Here, we examine systematically the effect of different choices in the values of key parameters from data acquisition through statistical testing on the inference of the selectivity of individual neurons for task states. We do so by using as an experimental testbed, neuronal calcium dynamics imaged in the medial prefrontal cortex of freely behaving mice engaged in a classic exploration-avoidance task involving spontaneous (animal-controlled) state transitions - navigation in the elevated zero maze (EZM). We report that a number of key variables in this pipeline substantially impact the selectivity label assigned to neurons, and do so in distinct ways. By quantitatively comparing newly defined accuracy and robustness metrics for all the 128 possible combinations of levels of the key parameters, we discover in a data-driven manner, two optimal combinations that reliably characterize neuronal selectivity - one using discrete calcium events and another using continuous calcium traces. This work establishes objective and standardized parameter settings for reliable, calcium imaging-based investigations into the neural encoding of task-states.

neuroscience↗

bioRxiv2024

Benchmarking open access publication rates for the pharmaceutical industry and research-intensive academic institutions

BackgroundIn biomedical and health sciences, many articles are published open access (OA). OA publication rates continue to grow, especially for pharmaceutical research. Previous analyses of pharmaceutical OA publication rates were labor-intensive and not easily automated. We aimed to create a free, live, online dashboard comparing OA publication rates between pharmaceutical companies and academic institutions. MethodsUsing the Lens - an online platform aggregating full-text content and metadata for over 280 million scholarly works - we built a dashboard showing OA publication rates for medical research articles by authors from the top 40 pharmaceutical companies (pharma) and 40 research-intensive academic institutions (academia). The dashboard details OA rates by model, license and therapy area across three time frames: 12-24 months; 0-12 months; 0-10 years. We downloaded data from the dashboard between 24 July and 4 August 2023 and performed further analysis. ResultsOf the articles published 12-24 months before data extraction, 76.6% by pharma and 69.5% by academia were OA. The most common OA models were gold (pharma, 37%; academia, 41%) and hybrid (pharma, 22%; academia, 11%). Oncology had lower rates of OA articles than other therapy areas. In the 10 years before data extraction, growth in the OA publication rate was generally more rapid for pharmaceutical companies than for academic institutions, regardless of field (change in overall % OA 2013-2023: pharma, 3.1; academia, 1.6). ConclusionsThis dashboard provides novel and regularly updated evidence on the comparative OA publication practices of pharmaceutical companies and academic institutions. In our snapshot analysis, the OA publication rate was higher for pharmaceutical companies than for academic institutions and continues to increase. Notable differences were observed in approaches, in terms of licenses and OA models, which may reflect different institutional practices and circumstances. We encourage others to use this open resource for new research and to report their results.

scientific communication and education↗

bioRxiv2020

Phenotypic changes of bacteria through opportunity and global methylation leads to antibiotic resistance

The antibiotic stress on bacteria leads to initiation of adaptive mechanisms, including exploiting the available opportunity, if any, for cell survival. In order to use the opportunity for survival while under threat, the microbe undergoes various mechanisms which are not completely known e.g. homologous recombination, horizontal gene transfer etc. Our aim is to understand the adaptive mechanism for cell survival during stress, especially antibiotic stress, in E. coli in the presence of opportunity. Understanding this mechanism in bacteria that gained resistance will help in identifying alternative survival pathways. By subjecting a recombination deficient ({Delta}RecA) strain of bacteria to antibiotic stress, we expected cell death, due to its inability to repair DNA damage (1, 2). Here we show that providing an opportunity in the form of an antibiotic resistance gene with homologous ends aids bacterial survival. There was 3-fold increase in cell envelope thickness along with 2.5-fold increase in phosphatidylethanolamine (PE) content, and enhanced antibiotic resistance to >4000{micro}g/mL (Kan). We observed genome-wide alteration of methylation pattern that lead to changes in transcriptome, proteome, lipidome, and metabolite level, thus, leading to morphological and physiological changes. We prove that global methylation helps in survival of bacteria under stress that changes essential pathways like energy, cell envelope, lipids, amino acids acid, etc. leading to over production of cell wall components including synthesis of PE. By inhibiting the activity of methyltransferase, it is noticed that there is reduction in PE synthesis in agreement with demethylation. This proves that the phenotypic changes are caused due to the global methylation, and also demonstrates that demethylation could be used as a strategy to prevent antibiotic resistance in microbes. One Sentence SummaryGlobal methylation determines the survival of bacteria to gain the antimicrobial resistance with an opportunity

microbiology↗