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Nielsen, A. M.

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

4 recordsLinked to original sources

Glucocorticoids desensitize CRH neurons to norepinephrine via rapid nitrosylation-dependent regulation of α1 adrenoreceptor trafficking

Noradrenergic afferents to hypothalamic corticotropin releasing hormone (CRH) neurons provide a major excitatory drive for somatic stress activation of the hypothalamic-pituitary-adrenal (HPA) axis. We showed that glucocorticoids rapidly desensitize CRH neurons to norepinephrine and suppress inflammation-induced HPA activation via a glucocorticoid receptor- and endocytosis-dependent mechanism. Here, we show that 1 adrenoreceptor (AR1) trafficking is regulated by convergent glucocorticoid and nitric oxide synthase signaling mechanisms. Live-cell imaging of AR1b-eGFP-expressing hypothalamic cells revealed rapid corticosterone-stimulated redistribution of internalized AR1 from rapid recycling endosomes to late endosomes and lysosomes via a nitrosylation-regulated mechanism. Proximity assay demonstrated interaction of glucocorticoid receptors with AR1b and {beta}-arrestin, and showed corticosterone blockade of norepinephrine-stimulated AR1b/{beta}-arrestin interaction, which may prevent AR1b from entering the rapid recycling endosomal pathway. These findings demonstrate a rapid glucocorticoid regulation of G protein-coupled receptor trafficking and provide a molecular mechanism for rapid glucocorticoid desensitization of noradrenergic signaling in CRH neurons.

neuroscience↗

Chloroplast DNA methylation in the kelp Saccharina latissima is determined by origin and influenced by cultivation

DNA cytosine methylation is an important epigenetic mechanism in genomic DNA, but absent in the chloroplast DNA of most land plants. We detected methylation in the chloroplast DNA of the kelp Saccharina latissima, a non-model macroalgal species of high ecological (wild populations) and economic importance. Since the functional role of the chloroplast methylome is yet largely unknown, we compared for the first time the chloroplast DNA cytosine methylation between wild and cultured kelp from different climatic origins (High- Arctic (79 {degrees}N) and temperate (54 {degrees}N), laboratory samples at 5 {degrees}C, 10 {degrees}C and 15 {degrees}C). Our results suggest genome-wide differences in methylated sites, and methylation level, between the origins, and a strong effect of cultivation. Functions related to photosynthesis showed differential methylation only between origins. Significant differences in methylation between cultivated and wild samples of genes related to transcription and translation were unique to the high-arctic samples. Both findings indicate that origin and cultivation strongly, but differently affect the chloroplast methylome. Similar methylomes for samples from the same origin - independent from whether they grow in the wild or in the lab - suggest that origin- specific methylation marks on the chloroplast genome are inherited. Given that DNA- methylation affects gene expression, our study suggests that lab-cultivation alters epigenetically determined kelp chloroplast characteristics at least to the same degree as ecotypic differentiation does, but likely on a much shorter timescale. This indicates the capacity for rapid non-genetic adaptation in the kelp Saccharina latissima.

genomics↗

Masked features of task states found in individual brain networks

Completing complex tasks requires that we flexibly integrate information across brain areas. While studies have shown how functional networks are altered during different tasks, this work has generally focused on a cross-subject approach, emphasizing features that are common across people. Here we used extended sampling "precision" fMRI data to test the extent to which task states generalize across people or are individually-specific. We trained classifiers to decode state using functional network data in single-person datasets across 5 diverse task states. Classifiers were then tested on either independent data from the same person or new individuals. Individualized classifiers were able to generalize to new participants. However, classification performance was significantly higher within a person, a pattern consistent across model types, people, tasks, feature subsets, and even for decoding very similar task conditions. Notably, these findings also replicated in a new independent dataset. These results suggest that individual-focused approaches can uncover robust features of brain states, including features obscured in cross-subject analyses. Individual-focused approaches have the potential to deepen our understanding of brain interactions during complex cognition. Citation Diversity StatementRecently, the field of neuroscience has reported a bias in citation practices such that papers from minority groups are more often under-cited relative to the number of papers in the field (Dworkin et al. 2020). The authors of this paper were proactive in consideration of selecting references that reflect diversity of the field in thought, contribution, and gender. Utilizing previously derived databases (Dworkin et al. 2020; Zhou et al. 2020) we obtained the predicted gender of authors referenced in this manuscript. By this measure (and excluding self-citations to the first and last authors of our current paper), our references contain 13.87% woman(first)/woman(last), 23.3% man/woman, 23.3% woman/man, and 39.53% man/man. This method is limited in that a) names, pronouns, and social media profiles used to construct the databases may not, in every case, be indicative of gender identity and b) it cannot account for intersex, non-binary, or transgender people. Second, we obtained the predicted racial/ethnic category of the first and last author of each reference by databases that store the probability of a first and last name being carried by an author of color(Ambekar et al. 2009). By this measure (and excluding self-citations), our references contain 10.83% author of color (first)/author of color(last), 10.64% white author/author of color, 23.55% author of color/white author, and 54.98% white author/white author. This method is limited in that a) names and Florida Voter Data to make the predictions may not be indicative of racial/ethnic identity, and b) it cannot account for Indigenous and mixed-race authors, or those who may face differential biases due to the ambiguous racialization or ethnicization of their names. We look forward to future work that could help us to better understand how to support equitable practices in science.

neuroscience↗

Human Fronto-Striatal Connectivity is Organized into Discrete Functional Subnetworks

The striatum is interconnected with the cerebral cortex via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate cortico-striatal connections can be precisely mapped using invasive tract-tracing. However, noninvasive human research has not mapped these connections with anatomical precision, limited by the practice of averaging neuroimaging data across individuals. Here we utilized highly-sampled resting-state functional connectivity MRI for individually-specific precision functional mapping of cortico-striatal connections. We identified ten discrete, individual-specific subnetworks linking cortex--predominately frontal cortex--to striatum. These subnetworks included previously unknown striatal connections to the human language network. The discrete subnetworks formed a stepped rostral-caudal gradient progressing from nucleus accumbens to posterior putamen; this organization was strongest for projections from medial frontal cortex. The stepped gradient organization fit patterns of fronto-striatal connections better than a smooth, continuous gradient. Thus, precision subnetworks identify detailed, individual-specific stepped gradients of cortico-striatal connectivity that include human-specific language networks.

neuroscience↗