Biology subjects

Taylor, J. R.

Publications and source records attributed to Taylor, J. R..

7 recordsLinked to original sources

bioRxiv2026

A single cooperative experience increases corticolimbic synaptic density and prosocial behavior

Cooperation is typically studied as an output of the social brain, as opposed to an experience that shapes it. Here, we developed a task in rats that permits interaction while requiring joint action for reward. Cooperation depended on dyad familiarity and visual access. Anterior cingulate cortex (ACC) to basolateral amygdala (BLA) projections were activated during cooperation with a familiar partner, whereas ACC to anterior insula (AI) projections were simultaneously suppressed regardless of familiarity. A single 90 min cooperative experience increased presynaptic marker SV2A, detected by positron emission tomography (PET), in the amygdala and insula one day later. Concurrently, rodents demonstrated heightened attention toward a distressed conspecific. Cooperation is thus an experience that recruits dissociable corticolimbic pathways and changes brain and behavior beyond the encounter itself.

neuroscience↗

bioRxiv2026

Conserved Transcriptomic Signatures of Sirt6 Activity: A Cross-Species RNA-seq Meta-analysis

The NAD+-dependent histone deacetylase Sirt6 regulates transcription of multiple classes of genes, including those involved in metabolism, immune response, oxidative stress response, and development. Defining the Sirt6-regulated transcriptome is relevant to understanding the various important physiological roles of Sirt6, such as extending lifespan, maintaining metabolic health, and tumor suppression. Numerous studies have identified Sirt6 target genes, using both targeted and genome-wide approaches; however, consensus is limited and there has yet to be a systematic analysis of gene expression changes induced by altering Sirt6 levels. In the present study, we conducted a meta-analysis of 19 mammalian RNA-seq datasets in which Sirt6 levels were perturbed (knockout, knockdown, or overexpression). Our analyses included Gene Set Enrichment Analysis, pathway analysis of differentially expressed genes, and identification of individual differentially expressed genes. Our analysis identified consistent gene expression changes associated with lowering Sirt6 levels, including increased expression of immune response and ribosomal protein genes and reduced expression of lipid oxidation and oxidative phosphorylation genes. Extracellular Matrix and E2F target genes also had consistently increased expression upon Sirt6 reduction, highlighting novel regulation by Sirt6. To determine the conservation of gene regulation by Sirt6, we performed additional RNA-Seq meta-analysis on tissues from Drosophila melanogaster with Sirt6 deletion and overexpression. The fly datasets produced similar results to the mammal results, except for lipid oxidation genes, which were found to increase in Sirt6-low conditions. These results provide consensus about conserved and novel pathways transcriptionally regulated by Sirt6.

genomics↗

bioRxiv2025

The NMDAR positive allosteric modulator NYX-783 selectively blocks opioid withdrawal conditioned place aversion in mice.

Rates of opioid use disorder (OUD) and overdose deaths have increased dramatically in recent years. Currently approved medications for OUD include the opioid agonists methadone and buprenorphine, and the opioid antagonist naltrexone. However, relapse rates are high due to an impaired ability for addicts to control their urge to consume due to strong cravings, and the extreme severity of withdrawal symptoms. Additionally, the nature of the agonists can lead to abuse of those compounds as well. Non-opioid targets, such as glutamate receptors, are potentially ideal for developing intervention strategies with the goal of reducing OUD, relapse, and overdose death. NYX-783 is a small molecule positive allosteric modulator for the glutamate receptor NMDA. It has been shown to modulate learning and memory, both of which are impaired in drug addicts, and known play a role in relapse. Using mice, we have conducted preclinical studies to evaluate the potential for NYX-783 as a therapeutic for OUD with assessment of several outcomes: 1) respiratory depression, 2) consumption during maintenance of regular consumption as well as post-abstinence reinstatement, 3) motivation for consumption, 4) somatic withdrawals, and 5) the development of aversion to withdrawal symptoms. For respiratory depression studies, mice were pretreated 1h prior with NYX-783 and respiratory rates were monitored for 15min after each escalating dose of oxycodone. No effects were seen for any dose of NYX-783. To test for effects on drug consumption, mice were trained to orally self-administer oxycodone and then treated every two days with different doses of NYX-783 or entering an abstinence phase prior to testing with NYX-783. No effect on intake at clinically-relevant doses was observed during regular maintenance or post-abstinence intake. Additionally, we used a progressive ratio to assess the motivation self-administering mice had for reward acquisition, and no effect of NYX-783 was observed on rewards earned. We next evaluated withdrawal using two separate paradigms to test for effects of NYX-783 on, 1) for somatic withdrawal symptoms, 2) aversion to the state of withdrawal. For somatic withdrawal, using higher doses of naloxone (1 mg/kg), NYX-783 did not attenuate jumping behavior. For aversion to withdrawal, three aversion pairings were completed that consisted of oxycodone treatment, followed by NYX-783 preceding a low dose of naloxone (0.1mg/kg ip) immediately before pairing in a specific context. These alternated with neutral (saline) pairings daily. We observed a significant improvement in aversion scores in female mice treated with NYX-783, and a trending significant improvement in males. This suggests a potential therapeutic use for NYX-783 in reducing the negative state of withdrawal that can drive relapse in OUD.

animal behavior and cognition↗

bioRxiv2022

Conserved reward-mediated, reinforcement-learning mechanisms in Pavlovian and instrumental tasks

Model-free and model-based computations are argued to distinctly update action values that guide decision-making processes. It is not known, however, if these model-free and model-based reinforcement learning mechanisms recruited in operationally based, instrumental tasks parallel those engaged by Pavlovian based behavioral procedures. Recently, computational work has suggested that individual differences in the attribution of incentive salience to reward predictive cues, i.e., sign- and goal-tracking behaviors, are also governed by variations in model-free and model-based value representations that guide behavior. Moreover, it is not appreciated if these systems that are characterized computationally using model-free and model-based algorithms are conserved across tasks for individual animals. In the current study, we used a within- subject design to assess sign-tracking and goal-tracking behaviors using a Pavlovian conditioned approach task, and, then characterized behavior using an instrumental multi-stage decision-making (MSDM) task in rats. We hypothesized that both Pavlovian and instrumental learning processes may be driven by common reinforcement-learning mechanisms. Our data confirm that sign-tracking behavior was associated with greater reward-mediated, model-free reinforcement learning and that it was also linked to model-free reinforcement learning in the MSDM task. Computational analyses revealed that Pavlovian model-free updating was correlated with model-free reinforcement learning in the MSDM task. These data provide key insights into the computational mechanisms mediating associative learning that could have important implications for normal and abnormal states. Significance StatementModel-free and model-based computations that guide instrumental, decision-making processes may also be recruited in Pavlovian based behavioral procedures. Here, we used a within-subject design to test the hypothesis that both Pavlovian and instrumental learning processes were driven by common reinforcement-learning mechanisms. Sign- tracking and goal-tracking behaviors were assessed in rats using a Pavlovian conditioned approach task, and, then instrumental behavior characterized using a multi- stage decision-making (MSDM) task. We report that sign-tracking behavior was associated with greater model-free, but not model-based, learning in the MSDM task. These data suggest that Pavlovian and instrumental behaviors are driven by conserved reinforcement-learning mechanisms.

animal behavior and cognition↗

bioRxiv2020

Entraining alpha activity using visual stimulation in patients with chronic musculoskeletal pain. A feasibility study.

Entraining alpha activity with rhythmic visual, auditory, and electrical stimulation can reduce experimentally induced pain. However, evidence for alpha entrainment and pain reduction in patients with chronic pain is limited. This feasibility study investigated whether visual alpha stimulation can increase alpha power in patients with chronic musculoskeletal pain and secondarily, if chronic pain was reduced following stimulation. In a within-subject design, 22 patients underwent 4-minute periods of stimulation at 10 Hz (alpha), 7 Hz (high-theta, control), and 1 Hz (control) in a pseudo-randomized order. Patients underwent stimulation both sitting and standing and verbally rated their pain before and after each stimulation block on a 0-10 numerical rating scale. Global alpha power was significantly higher during 10 Hz compared to 1 Hz stimulation when patients were standing (t = -6.08, p <.001). On a more regional level, a significant increase of alpha power was found in the right-middle and left-posterior region when patients were sitting. With respect to our secondary aim, no significant reduction of pain intensity and unpleasantness was found. However, only the alpha stimulation resulted in a minimal clinically important difference in at least 50% of participants for pain intensity (50%) and unpleasantness ratings (65%) in the sitting condition. This study provides initial evidence for the potential of visual stimulation as a means to enhance alpha activity in patients with chronic musculoskeletal pain. The brief period of stimulation was insufficient to reduce chronic pain. This study is the first to provide evidence that a brief period of visual stimulation at alpha frequency can significantly increase alpha power in patients with chronic musculoskeletal pain. Further study is warranted to investigate optimal dose and individual stimulation parameters to achieve pain relief in these patients.

neuroscience↗

bioRxiv2020

Expecting the unexpected: the paranoid style of belief updating across species

Paranoia is the belief that harm is intended by others. It may arise from selective pressures to infer and avoid social threats, particularly in ambiguous or changing circumstances. We propose that uncertainty may be sufficient to elicit learning differences in paranoid individuals, without social threat. We used reversal learning behaviour and computational modelling to estimate belief updating across individuals with and without mental illness, online participants, and rats exposed to chronic methamphetamine, an elicitor of paranoia in humans. Paranoia is associated with a strong but immutable prior on volatility, accompanied by elevated sensitivity to perceived changes in the task environment. Methamphetamine exposure in rats recapitulates this impaired uncertainty-driven belief updating and rigid anticipation of a volatile environment. Our work provides evidence of fundamental, domain-general learning differences in paranoid individuals. This paradigm enables further assessment of the interplay between uncertainty and belief-updating across individuals and species.

neuroscience↗

bioRxiv2019

A framework for the development of a global standardised marine taxon reference image database (SMarTaR-ID) to support image-based analyses

Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure follows the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem.

ecology↗