Biology subjects

White, A. M.

Publications and source records attributed to White, A. M..

10 recordsLinked to original sources

bioRxiv2025

Estrogen Receptor Beta Localized on Ventral Tegmental Area Dopamine Neurons Regulates Nicotine Self-Administration Acquisition in Ovary-Intact Female Rats

Women exhibit greater nicotine use vulnerability than men. High estradiol (E2) exacerbates nicotine use outcomes in women, effects which have been modeled in preclinical nicotine self-administration (SA) studies. Nicotine SA is maintained by dopamine (DA) release from the ventral tegmental area (VTA) to the nucleus accumbens (NA). E2 exerts its effects by binding to estrogen receptors (ER), including ER, ER{beta}, and G-protein coupled ER-1 (GPER-1)s. E2 action at ERs specifically has been shown to potentiate DA neuronal excitability within the VTA. Further, we have shown that ovariectomy decreases both nicotine use during SA and VTA ER{beta} protein. Despite clear evidence of mechanistic relationships between E2, ERs, DA, and nicotine, no studies to date have functionally evaluated the specific role of ER{beta} located on VTA DA cells in driving nicotine consumption during SA in females. There are currently no tools that allow for evaluations of relationships between nicotine neurobiology and ERs with cell-type specificity, as ER{beta} is also localized on other (non-DA) cell types within the VTA. As such, the goals of the present studies were (1) to build and validate a novel adeno-associated viral construct that produces long-term knockdown of ER{beta} specifically on VTA DA neurons, and (2) to determine if VTA DA ER{beta} viral knockdown reduces nicotine SA in ovary-intact female rats. Here we show that ER{beta} regulates VTA DA neuron excitability, and that ER{beta} knockdown in VTA DA neurons reduces DA neuron firing frequency. We also show that VTA ER{beta} knockdown in DA neurons reduces nicotine SA acquisition in ovary-intact female rats. Together, our results demonstrate a critical role of ER{beta} in driving nicotine use in females, underscoring the need for future studies to evaluate neurobehavioral mechanisms of smoking through the lens of sex differences.

neuroscience↗

bioRxiv2025

Utility of the Recombinase Driver CX3CR1::Cre Rat Strain to Evaluate Microglial Contributions to Nicotine Addiction

Smoking remains a leading preventable cause of death, and nicotine is the primary substance responsible for maintaining use of tobacco products. Preclinical rodent models have shown that neuroimmune signaling is dysregulated by nicotine self-administration (SA) within the nucleus accumbens core (NAcore), which is a key region within the mesolimbic brain reward pathway. Microglia are the resident brain immune cell and prior studies have shown that they play an important role in nicotine-related behaviors. However, while there are transgenic mouse lines that allow for specific evaluations of microglia to neurobiology and behavior, there are fewer tools available for rats as a model species thus limiting our ability to evaluate specific contributions of microglia to nicotine SA. Using transgenic rats expressing Cre under the control of the CX3CR1 promoter bred on a Long Evans (LE) background, we show that NAcore microglia can be specifically transduced with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). We further show that CX3CR1::Cre rats readily self-administer nicotine, and display a characteristic extinction curve that is not different from outbred LE or Cre-negative littermates. Together, these validation studies lay the foundation for future use of this transgenic rat line to evaluate the specific contributions of microglia in the brain to neurobehavioral underpinnings of nicotine addiction.

neuroscience↗

bioRxiv2025

C. elegans food choice exhibits effort discounting-like behavior

Cost-benefit decisions are ubiquitous in both human and animal behavior. Economists have developed formal models of cost-benefit decision-making by focusing on discounting behavior, the devaluation of a reward based on the costs associated with it. The phylogenetic limits of discounting behavior remain unknown. Here, we provide evidence that the nematode C. elegans exhibits behavior closely resembling effort discounting. Given a choice between food options that are easy or difficult to consume, worms devalue the latter in a manner predicted by economic models. We identified a plausible mechanism for this behavior based on differential rates of leaving food patches and demonstrated that this mechanism is disrupted by deficits in dopamine signaling, as in rodents. Together, these results establish C. elegans as a potential invertebrate model for discounting behavior and set new phylogenetic bounds on this type of cost-benefit decision-making.

animal behavior and cognition↗

bioRxiv2023

Theory and practice of using cell strainers to sort Caenorhabditis elegans by size

The nematode Caenorhabditis elegans is a model organism widely used in basic, translational, and industrial research. C. elegans development is characterized by five morphologically distinct stages, including four larval stages and the adult stage. Stages differ in a variety of aspects including size, gene expression, physiology, and behavior. Enrichment for a particular developmental stage is often the first step in experimental design. When many hundreds of worms are required, the standard methods of enrichment are to grow a synchronized population of hatchlings for a fixed time, or to sort a mixed population of worms according to size. Current size-sorting methods have higher throughput than synchronization and avoid its use of harsh chemicals. However, these size-sorting methods currently require expensive instrumentation or custom microfluidic devices, both of which are unavailable to the majority C. elegans laboratories. Accordingly, there is a need for inexpensive, accessible sorting strategies. We investigated the use of low-cost, commercially available cell strainers to filter C. elegans by size. We found that the probability of recovery after filtration as a function of body size for cell strainers of three different mesh sizes is well described by logistic functions. Application of these functions to predict filtration outcomes revealed non-ideal properties of filtration of worms by cell strainers that nevertheless enhanced filtration outcomes. Further, we found that serial filtration using a pair of strainers that have different mesh sizes can be used to enrich for particular larval stages with a purity close to that of synchronization, the most widely used enrichment method. Throughput of the cell strainer method, up to 14,000 worms per minute, greatly exceeds that of other enrichment methods. We conclude that size sorting by cell strainers is a useful addition to the array of existing methods for enrichment of particular developmental stages in C. elegans.

bioengineering↗

bioRxiv2022

Expanded diversity of tfdA harboring bacteria across the natural and built environment

2,4-Dichlorophenoxyacetic acid (2,4-D) is an herbicide commonly used in aquatic and terrestrial environments that is degraded by bacteria through the TFD pathway. Previous work has relied on culture-based methods to develop primers for qPCR analysis of the gene cassette in environmental samples. In this study, we combined molecular and genomic approaches to examine the accuracy of established tfdA qPCR primers on environmental samples and update the phylogeny of tfdA genes detected in bacterial genomes. We found most putative 2,4-D degraders are within the Proteobacteria but also found several novel degraders including members of the phyla Candidatus Rokubacteria and Candidatus Eremiobacteraeota. In silico analysis of established primers showed potential amplification of < 5% of putative degrader sequences but 52-100% of experimentally verified degraders when allowing for three and one mismatches between template and primer sequences, respectively. Overall, our work expands the diversity of putative 2,4-D degraders and demonstrates the limitations of culture-based tools for investigating functional diversity of microorganisms in the environment. ImportanceCultivation-based methods can misrepresent the diversity of environmental microorganisms. Our work showcases one example of how culture-based development of molecular tools underestimates the full spectrum of 2,4-D degrading microorganisms. Accurately identifying microorganisms with 2,4-D degradation potential is crucial for understanding the biodegradation potential of a commonly used herbicide across terrestrial, aquatic, and subsurface environments. Additionally, this work reinforces well-documented pitfalls associated with relying on cultured representatives when constructing primers and the challenges of translating findings from a few cultured representatives to understudied or unknown microorganisms in complex environments.

microbiology↗

bioRxiv2022

Intact maternal buffering of stress response in infant rats despite altered responsivity towards maternal olfactory cues in the valproic acid model of autism-like behavior

Disrupted processing of social cues and altered social behaviors are among the core symptoms of autism spectrum disorders (ASDs), and they emerge as early as the first year of life. These differences in sensory abilities may affect the ability of children with ASDs to securely attach to a caregiver and experience caregiver buffering of stress. Prenatal exposure to valproic acid (VPA) has been used to model some aspects of ASDs in rodents. Here, we asked whether prenatal VPA exposure altered infant rats behavioral responsivity to maternal olfactory cues in an odor preference test and affected maternal buffering of infants stress responsivity to shock. In the odor preference test, one-week old rats treated with VPA during pregnancy appeared to have impaired social recognition and/or may be less motivated to approach social odors in early infancy. These effects were particularly prominent in female pups. In two-week old rats, VPA-exposed pups and saline-exposed pups showed similar preferences for home cage bedding. Although VPA-exposed pups may initially have a deficit in this attachment-related behavior they do recover typical responses to home cage bedding in later infancy. Both control and VPA-exposed pups showed robust stress hormone responses to repeated shocks, an effect which was blocked when a calm mother was present during shock exposure. No sex differences in the effect of maternal presence on the stress response to shock and no interactions between sex and prenatal drug exposure were observed. Although VPA-exposed pups may show impaired responsivity to maternal cues in early infancy, maternal presence is still capable of regulating the stress response in VPA-exposed pups. In this study we demonstrate the importance of utilizing multiple batteries of tests in assessing behavior, dissecting the behavior on one test into different components. Our results inform about the underlying behavioral characteristics of some of the ASD phenotypes, including sex differences reported by clinical studies, and could shed light on potential opportunities for intervention.

neuroscience↗

bioRxiv2022

Structural and functional analysis of the human Cone-rod homeobox transcription factor

The cone-rod homeobox (CRX) protein is a critical K50 homeodomain transcription factor responsible for the differentiation and maintenance of photoreceptor neurons in the vertebrate retina. Mutant alleles in the human gene encoding CRX result in a variety of distinct blinding retinopathies, including retinitis pigmentosa, cone-rod dystrophy, and Leber congenital amaurosis. Despite the success of using in vitro biochemistry, animal models, and genomics approaches to study this clinically relevant transcription factor over the past 24 years since its initial characterization, there are no high-resolution structures in the published literature for the CRX protein. In this study, we use bioinformatic approaches and small-angle x-ray scattering (SAXS) structural analysis to further understand the biochemical complexity of the human CRX homeodomain (CRX-HD). We find that the CRX-HD is a compact, globular monomer in solution that can specifically bind functional cis-regulatory elements encoded upstream of retina -specific genes. This study presents the first structural analysis of CRX, paving the way for a new approach to studying the biochemistry of this protein and its disease-causing mutant protein variants.

biochemistry↗

bioRxiv2021

Promoting long-term forest landscape resilience in the Lake Tahoe basin

Rapid environmental changes expected in the 21st century challenge the resilience of wildlands around the world. The western portion of the Lake Tahoe basin (LTW) in California is an important ecological and cultural hotspot that is at risk of degradation from current and future environmental pressures. Historical uses, fire suppression, and a changing climate have created forest landscape conditions at risk of drought stress, destructive fire, and loss of habitat diversity. We prospectively modeled forest landscape conditions for a period of 100 years to evaluate the efficacy of five unique management scenarios in achieving desired landscape conditions across the 23,600 hectares of LTW. Management scenarios ranged from no management other than fire suppression to applying treatments consistent with historical fire frequencies and extent (i.e., regular and broadscale biomass reduction). We developed a decision support tool to evaluate environmental and social outcomes within a single framework to provide a transparent set of costs and benefits; results illuminated underlying mechanisms of forest resilience and provided actionable guidance to decision makers. Sixteen attributes were assessed in the model after assigning weights to each, derived through a survey of stakeholder priorities, so that the contribution of each attribute to evaluations of scenario performance was influenced by the combined priorities of stakeholders. We found that removing forest biomass across the landscape, particularly when accomplished using extensive fire-based removal techniques, led to highly favorable conditions for environmental quality and promoting overall landscape resilience. Environmental conditions resulting from extensive fire-based biomass removal also had nominal variation over time, in contrast with strategies that had less extensive and/or used physical removal techniques, namely thinning. Our analysis provided a transparent approach to data assessment, considering the priorities of stakeholders, to provide insights into the complexities of maintaining optimal conditions and managing landscapes to promote ecosystem resilience in a changing world.

ecology↗

bioRxiv2021

Early acquisition of threat conditioning in a selectively-bred anxiety-like rat phenotype: regulation by maternal presence and FGF2

Temperament is an innate, stable predisposition towards particular emotional and behavioral responses. In humans, certain temperaments are associated with a heightened risk of developing anxiety later in life. Non-human animals, including rodents, also exhibit innate, stable dispositions; these are referred to as behavioral phenotypes. The interaction between behavioral phenotype and early life adverse events is critical for the development of maladaptive anxiety. Rodent studies of typically developing animals have identified a number of mechanisms that protect against aversive experiences in early life. One such mechanism is an early life quiescence of threat learning, which protects against the effects of stress and facilitates safety and attachment learning. However, little is known about the factors that alleviate the effects of early life aversive events on phenotypes vulnerable to pathological anxiety. Here, we examined threat learning and the stress response in selectively-bred infant rats that show an anxiety-like phenotype relative to typically developing animals. We investigated the potential roles of maternal presence and the anxiolytic neurotrophic factor fibroblast growth factor 2 (FGF2) in regulating threat learning and the stress response in infant anxiety-like phenotype animals. We observed that rats selectively-bred for anxiety-like behaviors could acquire conditioned freezing earlier in life than typically developing animals. FGF2 administration on postnatal day 1 (PND 1) and maternal presence during threat conditioning were both capable of suppressing this early emergence of conditioned freezing. However, neither FGF2 nor maternal presence during threat conditioning were associated with reduced corticosterone levels during threat conditioning. Our results suggest that although an anxiety-like phenotype may be associated with early threat learning, environmental factors (such as maternal presence) and pharmacological intervention (such as modulation of the FGF2 system) may be capable of counteracting that early aversive learning. Interventions in vulnerable infants may thus decrease the impact of aversive events.

neuroscience↗

bioRxiv2019

United States wildlife and wildlife product imports from 2000-2014

The global wildlife trade network is a massive system that has been shown to threaten biodiversity conservation, introduce non-native species and pathogens, and cause chronic animal welfare concerns. Despite its scale and impact, comprehensive characterization of the global wildlife trade is hampered by data that are limited in their temporal or taxonomic scope and detail. To help fill this gap, we present data on 15 years of the importation of wildlife and their derived products into the United States (2000-2014), originally collected by the United States Fish and Wildlife Service. We curated and cleaned the data and added taxonomic information to improve data usability. These data include > 2 million wildlife or wildlife product shipments, representing > 60 biological classes and > 3.2 billion live organisms. These data will be broadly useful to both scientists and policymakers seeking to better understand the volume, sources, biological composition, and potential risks of the global wildlife trade.

ecology↗