Biology subjects

Kimble, V. M.

Publications and source records attributed to Kimble, V. M..

3 recordsLinked to original sources

bioRxiv2025

Brief disruption of the microbiome has age-dependent effects on morphine reward and gene expression in the medial prefrontal cortex of adolescent and adult mice

Adolescence is a critical period for the initiation of problematic drug use, which significantly increases the risk of developing substance use disorders later in life. This heightened vulnerability is partly attributed to the immaturity of the prefrontal cortex, a brain region both essential for decision-making and implicated in drug reward. During adolescence, peripheral systems, such as the gut microbiome, also undergo substantial changes. Emerging evidence suggests that disruptions to the gut microbiome can influence gene expression and drug reward behaviors in rodent models. In this study, we investigated the effects of microbiome disruption on morphine reward and prefrontal cortical gene expression in adolescent and adult mice. Using oral antibiotics to transiently disrupt the microbiome, we found that short-term antibiotic exposure reduced morphine place preference specifically in adolescent mice. In a separate cohort, we observed that antibiotic treatment altered the transcriptomic response to morphine in the medial prefrontal cortex across all age groups. Notably, the transcriptomic changes induced by antibiotics and morphine were age-specific, with distinct gene expression patterns observed in adolescents compared to adults. These findings establish a foundation for future research into the role of the gut microbiome in opioid reward and highlight potential gene pathways underlying age-dependent differences in opioid sensitivity.

neuroscience↗

bioRxiv2022

Trends in self-citation rates in neuroscience literature

Citation metrics influence academic reputation and career trajectories. Recent works have highlighted flaws in citation practices in the Neurosciences, such as the under-citation of women. However, self-citation rates--or how much authors cite themselves--have not yet been comprehensively investigated in the Neurosciences. This work characterizes self-citation rates in basic, translational, and clinical Neuroscience literature by collating 100,347 articles from 63 journals between the years 2000-2020. In analyzing over five million citations, we demonstrate four key findings: 1) increasing self-citation rates of Last Authors relative to First Authors, 2) lower self-citation rates in low- and middle-income countries, 3) gender differences in self-citation stemming from differences in the number of previously published papers, and 4) variations in self-citation rates by field. Our characterization of self-citation provides insight into citation practices that shape the perceived influence of authors in the Neurosciences, which in turn may impact what type of scientific research is done and who gets the opportunity to do it.

neuroscience↗

bioRxiv2020

Genetic variation and sex differences are missed opportunities for addiction biology.

Concerns about external validity of rodent models and translation of findings across species are often based on narrow investigations of populations with limited diversity. Sources of individual variation - including genetics and sex - are only infrequently encompassed in model organism studies. As with most complex diseases, risk for cocaine use disorder is subject to considerable inter-individual variation. Explicit inclusion of individual differences in rodent research may reveal conserved phenotypes and molecular systems relevant to human addiction. We surveyed cocaine-related traits in both males and females of eight inbred mouse strains whose genomes collectively capture 90% of the genetic diversity of the mouse species. Across these strains, individual differences explained a substantial proportion of variance in cocaine-responsive or cocaine response-predictive behavioral and physiological phenotypes. Wild-derived mouse strains often extended the phenotypic ranges of these behaviors beyond what is observed in conventional laboratory strains. Striatum transcriptional responses to cocaine were also highly dependent upon strain and sex differences; most cocaine-responsive genes were differentially expressed in a manner moderated by strain, sex, or their combination. We compared the strain- and sex-mediated transcriptional responses to cocaine in mice to transcriptomic analysis of people with cocaine use disorder and found that mouse similarity to humans was highly dependent upon mouse genetic background and sex. Specifically, male WSB/EiJ mice and female NOD/ShiLtJ mice exhibited the greatest degree of neural transcriptional consilience with humans with cocaine use disorder. Model organism diversity thus represents a crucial source of biological information that can substantially improve external validity of neuropsychiatric research. Significance StatementLaboratory mice are widely used in research on neurobiological mechanisms of addiction, but most studies use a single strain and often sex of mice. To assess how individual differences in mice modulate addiction-related traits and how this impacts comparative analysis with humans, we studied cocaine-relevant behaviors and brain molecular correlates in both males and females of genetically diverse mouse strains. In this population, individual differences related to sex and/or genetics explain large proportions of differences in cocaine-related traits. Importantly, brain gene expression data demonstrated that some strains mimic human genomic states more readily than others. Individual differences thus represent a crucial and underdeveloped source of biological information about addiction mechanisms that may influence the translational utility of such studies.

neuroscience↗