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Blount, A.

Publications and source records attributed to Blount, A..

3 recordsLinked to original sources

RGS6 regulates Kappa Opioid Receptor-mediated antinociceptivebehaviors

Targeting the kappa opioid receptor (KOR) system has emerged as a potential alternative to current analgesics, however, advancing the therapeutic development of KOR requires further elucidation of its intracellular signaling events and modulators. Among these intracellular modulators, Regulators of G protein signaling (RGS) proteins act as key modulators of GPCR signaling to shape nociceptive circuits and influence pain processing. Despite this, the molecular diversity of RGS proteins that shape KOR signaling and its behavioral consequences remains largely unexplored. Here we report that RGS6, a member of the R7 RGS family, is highly expressed in nociceptive areas and modulates multiple modalities of KOR-dependent anti-nociception and nocifensive behaviors. Using global single and double knockout mouse models we show that this anti-nociceptive phenotype was highly specific to RGS6 within the R7 RGS family. Further we demonstrate that the R7 RGS family displays a lack of functional redundancy in regulation of KOR signaling and behaviors. Using peripherally restricted KOR agonists, we found that KOR-RGS6 anti-nociceptive signaling displays sex differences in a site-specific manner, as females but not males displayed enhanced anti-nociceptive and blunted nocifensive behaviors. Our findings suggest that RGS6 is a highly specific modulator of KOR-dependent anti-nociceptive signaling and plays an essential role in modulating nociceptive circuits, potentially aiding in the development of novel analgesic drugs and therapeutics.

pharmacology and toxicology↗

Comparison of Three Individual Identification Algorithms for Sperm Whales (Physeter macrocephalus) after Automated Detection

Photo-identification of individual sperm whales (Physeter macrocephalus) is the primary technique for mark-recapture-based population analyses for the species The visual appearance of the fluke -- with its distinct nicks and notches -- often serves as the primary visual differentiator, allowing humans to make recorded sightings of specific individuals. However, the advent of digital photography and the significant increase in volume of images from multiple projects in combination with pre-existing historical catalogs has made applying the method more challenging.with the required human labor for de-duplication (reduction of Type II errors) and reconciliation of sightings between large datasets too cost- and time-prohibitive. To address this, we trained and evaluated the accuracy of PIE v2 (a triplet loss network) along with two existing fluke trailing edge-matching algorithms, CurvRank v2 and Dynamic Time Warping (DTW), as a mean to speed comparison among a high volume of photographs. Analyzed data were collected from a curated catalog of well-known sperm whales sighted across years (2005-2018) off the island of Dominica. The newly-trained PIE model outperformed the older CurvRank and DTW algorithms, and PIE provided the following top-k individual ID matching accuracy on a standard min-3/max-10 sighting training data set: Rank-1: 87.0%, Rank-5: 90.5%, and Rank-12: 92.5%. An essential aspect of PIE is that it can learn new individuals without network retraining, which can be immediately applied in the presence of (and for the resolution of) duplicate individuals in overlapping catalogs. Overall, our results recommend the use of PIE v2 and CurvRank v2 for ID reconciliation in combination due to their complementary performance.

ecology↗

The effect of odor enrichment on olfactory acuity: Olfactometric testing in mice using two mirror-molecular pairs.

Intelligent systems in nature like the mammalian nervous system benefit from adaptable inputs that can tailor response profiles to their environment that varies in time and space. Study of such plasticity, in all its manifestations, forms a pillar of classical and modern neuroscience. This study is concerned with a novel form of plasticity in the olfactory system referred to as induction. In this process, subjects unable to smell a particular odor, or unable to differentiate similar odors, gain these abilities through mere exposure to the odor(s) over time without the need for attention or feedback (reward or punishment). However, few studies of induction have rigorously documented changes in olfactory threshold for the odor(s) used for "enrichment." We trained 36 CD-1 mice in an operant-olfactometer (go/no go task) to discriminate a mixture of stereoisomers from a lone stereoisomer using two enantiomeric pairs: limonene and carvone. We also measured each subjects ability to detect one of the stereoisomers of each odor. In order to assess the effect of odor enrichment on enantiomer discrimination and detection, mice were exposed to both stereoisomers of limonene or carvone for 2 to 12 weeks. Enrichment was effected by adulterating the subjects food (passive enrichment) with one pair of enantiomers or by exposing them to the enantiomers in daily operant discrimination testing (active enrichment). We found that neither form of enrichment altered discrimination nor detection. And this result pertained using either within-subject or between-subject experimental designs. Unexpectedly, our threshold measurements were among the lowest ever recorded for any species, which we attributed to the relatively greater amount of practice (task replication) we allowed our mice compared to other reports. Interestingly, discrimination thresholds were no greater (limonene) or only modestly greater (carvone) from detection thresholds suggesting chiral-specific olfactory receptors determine thresholds for these compounds. The super-sensitivity of mice, shown in this study, to the limonene and carvone enantiomers, compared to the much lesser acuity of humans for these compounds, reported elsewhere, may resolve the mystery of why the former group with four-fold more olfactory receptors have tended, in previous studies, to have similar thresholds to the latter group. Finally, our results are consistent with the conclusion that supervised-perceptual learning i.e. that involving repeated feedback for correct and incorrect decisions, rather than induction, is the form of plasticity that allows animals to fully realize the capabilities of their olfactory system.

neuroscience↗