Biology subjects

Pires, A.

Publications and source records attributed to Pires, A..

3 recordsLinked to original sources

bioRxiv2020

Establishment of Multi-stage Models of Drug Taking and Seeking in Mice

A genetically tractable animal model would provide a needed strategy to resolve the biological basis of drug addiction. Intravenous self-administration (IVSA) is the gold standard for modeling cocaine and opioid addiction in animals, but technical limitations have precluded the widespread use of IVSA in mice. Here, we describe the first IVSA paradigms for mice that capture the multi-stage nature of the disease and permit predictive modeling. Mice with long-standing indwelling jugular catheters engaged in cocaine or opioid-associated lever responding that was fixed ratio- and dose-dependent, extinguished by the withholding of drug, and reinstated by the presentation of paired cues. Machine learning revealed that vulnerability to drug seeking and relapse were predicted by a mouses a priori response to novelty, sensitivity to drug-induced locomotion, and drug-taking behavior. Application of this behavioral and analysis approach to genetically-engineered mice will facilitate the identification of the neural circuits driving addiction susceptibility and relapse and focused therapeutic development.

neuroscience↗

bioRxiv2020

The marine gastropod Crepidula fornicata remains resilient to ocean acidification across two life history stages

Rising atmospheric CO2 reduces seawater pH causing ocean acidification (OA). Understanding how resilient marine organisms respond to OA may help predict how community dynamics will shift as CO2 continues rising. The common slipper shell snail Crepidula fornicata is a resilient marine gastropod native to eastern North America, which has been a successful invader along the western European coastline and elsewhere. To examine its potential resilience to OA, we conducted two controlled laboratory experiments. First, we examined several phenotypes and genome-wide gene expression of C. fornicata in response to pH treatments (7.5, 7.6, 8.0) throughout the larval stage and then tested how conditions experienced as larvae influenced juvenile stages (i.e. carryover effects). Second, we examined genome-wide gene expression patterns of C. fornicata larvae in response to acute (4, 10, 24 and 48 hours) pH treatment (7.5, 8.0). Both C. fornicata larvae and juveniles exhibited resilience to OA and gene expression responses highlight the role of transcriptome plasticity in OA resilience. Larvae did not exhibit reduced growth under OA until they were at least 4 days old. These phenotypic effects were preceded by broad transcriptomic changes, which likely serve as an acclimation mechanism for combating reduced pH conditions frequently experienced in littoral zones. Delayed metamorphosis was observed for larvae reared at reduced pH. Although juvenile size reflected larval rearing pH conditions, no carryover effects in juvenile growth rates were observed. Transcriptomic analyses suggest increased metabolism under OA, which may indicate compensation in reduced pH environments. Time course transcriptomic analyses suggest energetic burdens experienced under OA eventually dissipate, allowing C. fornicata to reduce metabolic demands and acclimate to reduced pH. This study highlights the importance of assessing the effects of OA across life history stages and demonstrates how transcriptomic plasticity can allow highly resilient organisms, like C. fornicata, acclimate to reduced pH environments.

genomics↗

bioRxiv2018

Resilience of Atlantic Slippersnail Crepidula fornicata Larvae in the Face of Severe Coastal Acidification

Globally, average oceanic pH is dropping, and it will continue to decline into the foreseeable future. This ocean acidification (OA) will exacerbate the natural fluctuations in pH that nearshore ecosystems currently experience daily, potentially pushing marine organisms to their physiological limits. Adults of Crepidula fornicata (the Atlantic slippersnail) have proven remarkably resilient to many environmental changes, which is perhaps not surprising considering that they are common intertidally, have a geographically large native range, and have been extremely successful at invading coastal water in many other parts of the world. However, the larvae of C. fornicata have been shown to be somewhat more vulnerable than adults to the effects of reduced pH. Research to date has focused on the physiological impacts of OA on C. fornicata larvae; few studies have explored shifts in gene expression resulting from changes in pH. In the present study, we examined the response of young (4- day old) C. fornicata larvae to two extreme OA treatments (pH 7.5 and 7.6) relative to pH 8.0, documenting both phenotypic and genome-wide gene expression responses. We found that rearing larvae at reduced pH had subtle influences on gene expression, predominantly involving downregulation of genes related to growth and metabolism, accompanied by significantly reduced shell growth rates only for larvae reared at pH 7.5. Additionally, 10-day old larvae that had been reared at the two lower pH levels were far less likely to metamorphose within six hours when exposed to inducer. However, all larvae eventually reached similarly high levels of metamorphosis 24 hours after settlement induction. Finally, there were no observed impacts of OA on larval mortality. Taken together, our results indicate that far future OA levels have observable, but not severe, impacts on C. fornicata larvae, which is consistent with the resilience of this invasive snail across rapidly changing nearshore ecosystems. We propose that future work should delve further into the physiological and transcriptomic responses of all life history stages to gain a more comprehensive understanding of how OA impacts the intertidal gastropod C. fornicata.

molecular biology↗