Mapping Molecular Datasets Back to the Brain Regions They are Extracted from: Remembering the Native Countries of Hypothalamic Expatriates and Refugees

Khan, Arshad M.; Grant, Alice H.; Martínez, A.; Burns, Gully; Thatcher, Brendan S.; Anekonda, Vishwanath T.; Thompson, Benjamin; Roberts, Zachary S.; Moralejo, Daniel H.; Blevins, James E.

doi:10.1007/978-3-319-94593-4_6

Cited by 9 publications

(8 citation statements)

References 482 publications

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“…Future studies will employ single cell RNA‐seq to pinpoint which cells have been affected to the greatest extent by the selective breeding scheme as evidenced by the cell‐specific transcript changes. Our abilities to collect cell‐specific information in undisturbed landscapes in solid tissues is limited, but growing arsenal of omics techniques and precise brain‐mapping approaches provides a framework for these future studies. Performing brain cell‐specific activity analysis is critical for understanding complex processes underlying cognitive and behavioral functions.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions

Rosenfeld

Hekman

Johnson

et al. 2019

Genes Brain and Behavior

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The underlying neurological events accompanying dog domestication remain elusive. To reconstruct the domestication process in an experimental setting, silver foxes (Vulpes vulpes) have been deliberately bred for tame vs aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. The hypothalamus is an essential part of the hypothalamic-pituitary-adrenal axis and regulates the fight-or-flight response, and thus, we hypothesized that selective breeding for tameness/aggressiveness has shaped the hypothalamic transcriptomic profile. RNA-seq analysis identified 70 differentially expressed genes (DEGs). Seven of these genes, DKKL1, FBLN7, NPL, PRIMPOL, PTGRN, SHCBP1L and SKIV2L, showed the same direction expression differences in the hypothalamus, basal forebrain and prefrontal cortex. The genes differentially expressed across the three tissues are involved in cell division, differentiation, adhesion and carbohydrate processing, suggesting an association of

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Section: Discussionmentioning

confidence: 99%

Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions

Rosenfeld

Hekman

Johnson

et al. 2019

Genes Brain and Behavior

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“…A key goal of this study was to build upon and expand the prevailing literature by explicitly mapping patterns of neuronal activation to glycemic challenge using a standardized rat brain atlas. As we have argued previously [80, 98, 199, 200], the use of a standardized atlas to formally map cellular distributions affords investigators with the ability to examine multiple spatial datasets in a form that facilitates their direct comparison. We opted, as with all of our spatial mapping efforts for the rat ( e.g ., Refs.…”

Section: Discussionmentioning

confidence: 99%

Glycemic challenge is associated with the rapid cellular activation of the locus ceruleus and nucleus of solitary tract: Circumscribed spatial analysis of phosphorylated MAP kinase immunoreactivity

Tapia

Agostinelli

Chenausky

et al. 2022

Preprint

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Research using laboratory rats has shown that impaired glucose utilization or hypoglycemia is associated with cellular activation of neurons in the medulla (Winslow, 1733) (MY) that are implicated in the control of feeding behavior and hormonal counterregulatory responses. Changes in the activation of these neuronal populations are also associated with autonomic dysfunction that manifests itself in the form of blunted counterregulatory responses to repeated episodes of glucoprivation or hypoglycemia. An improved appreciation of the spatiotemporal dynamics of these medullary responses (and the phenotypes of the neurons responsible for them) could lead to the development of rational therapies or diagnostics to address patient complications associated with diabetes management, such as hypoglycemia-associated autonomic failure. At present, however, cellular-scale neural activation following glycemic challenge has been tracked in rodents primarily within hours of the challenge, rather than sooner, and these responses have been poorly mapped within standardized brain atlases in relation to the locations of cell types known to be present in the medulla and the larger Rhombic brain (His, 1893) (RB). Here, we report that within 15 min of receiving the glycemic challenge, 2-deoxy-D-glucose (2-DG; 250 mg/kg, i.v.), which is known to produce intracellular glucopenia and trigger glucoprivic feeding behavior, marked elevations were observed in the numbers of RB neuronal cell profiles immunoreactive for the cellular activation marker(s), phosphorylated p44/42 MAP kinases (phospho-ERK1/2). Dual immunostaining experiments showed that some, but not all, of these neurons were catecholaminergic, as identified by immunostaining for dopamine-beta-hydroxylase (DBH). To begin the process of mapping the locations of these rapidly-activated neurons in relation to known cytoarchitecture with standardized neuroanatomical nomenclature, we performed Nissl- and chemoarchitecture-based plane-of-section analysis to map their distributions at discrete rostrocaudal levels, along with associated basally-activated cholinergic and other catecholaminergic cell groups, within an open-access rat brain atlas. This analysis revealed that neurons of the locus ceruleus (Wenzel & Wenzel, 1812) (LC) and the nucleus of solitary tract (>1840) (NTS) displayed elevated numbers of phospho-ERK1/2+ neurons within 15 min following 2-DG administration. Notably, while catecholaminergic neurons co-labeled with phospho-ERK1/2 immunoreactivity, many non-catecholaminergic NTS neurons also displayed such activation. Both 2-DG and saline-treated groups also displayed phospho-ERK1/2+ neurons in the dorsal motor nucleus of vagus nerve (>1840), identified both by Nissl criteria and immunostaining for the cholinergic marker, choline acetyltransferase. Our results show that 2-DG-activation of certain RB catecholaminergic neurons is more rapid than perhaps previously realized, engaging neurons that serve multiple functional systems and are of varying cellular phenotypes. They also place these and other activated populations within standardized maps of cytoarchitectonically-defined RB regions, thereby streamlining their precise targeting and/or comparable mapping in preclinical rodent models of disease.

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“…These more traditional µCT datasets can be combined with whole-brain diceCT and region-of-interest histology to study structural anatomy across orders of magnitude in spatial scale that achieves ample coverage of external morphology and internal anatomy-resulting in a cell-to-skull hierarchy of data. Whether harnessed for model organisms (Cole 1944;Preuss 2000;Keifer and Summers 2016;Khan et al 2018), translational research (Bonnier et al 2014;Vazquez-Sanroman et al 2017;Kim et al 2019), or comparative neuroanatomical studies (Yartsev 2017), pipelines such as these hold great promise for unlocking data that can be unintentionally trapped by single-method preparations, especially those that do not adequately preserve deep internal soft tissues, such as the brain. To unlock general principles of nervous system organization across the tree of life (Butler and Hodos 2005;Manger et al 2008;Carlson 2012;Striedter et al 2014;Brenowitz and Zakon 2015;Russell et al 2017), highly integrative approaches, as we have demonstrated here, are essential (Schwenk et al 2009;Dowling et al 2010;Vogelstein et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Multiscale imaging of the rat brain using an integrated diceCT and histology workflow

et al. 2021

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Advancements in tissue visualization techniques have spurred signi cant gains in the biomedical sciences by enabling researchers to integrate their datasets across anatomical scales. Of particular import are techniques that enable the interpolation of multiple hierarchical scales in samples taken from the same individuals. This study demonstrates that two-dimensional histology techniques can be employed on neural tissues following three-dimensional diffusible iodine-based contrast-enhanced computed tomography (diceCT) without causing tissue degradation. This represents the rst step toward a multiscale pipeline for brain visualization. We studied brains from adolescent male Sprague-Dawley rats, comparing experimental (diceCT-stained then de-stained) to control (without diceCT) brains to evaluate neural tissues for immunolabeling integrity, compare somata sizes, and distinguish neurons from glial cells within the telencephalon and diencephalon. We hypothesized that if experimental and control samples do not differ signi cantly in quantitative metrics, brain tissues are robust to the chemical, temperature, and radiation environments required for these multiple, successive imaging protocols. Visualizations for experimental brains were rst captured via micro-computed tomography scanning of isolated, iodine-infused specimens. Samples were then cleared of iodine, serially sectioned, and prepared again using immuno uorescent, uorescent, and cresyl violet labeling, followed by imaging with confocal and light microscopy, respectively. Our results show that many neural targets are resilient to diceCT imaging and compatible with downstream histological staining as part of a low-cost, multiscale brain imaging pipeline.

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Mapping Molecular Datasets Back to the Brain Regions They are Extracted from: Remembering the Native Countries of Hypothalamic Expatriates and Refugees

Cited by 9 publications

References 482 publications

Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions

Hypothalamic transcriptome of tame and aggressive silver foxes (Vulpes vulpes) identifies gene expression differences shared across brain regions

Glycemic challenge is associated with the rapid cellular activation of the locus ceruleus and nucleus of solitary tract: Circumscribed spatial analysis of phosphorylated MAP kinase immunoreactivity

Multiscale imaging of the rat brain using an integrated diceCT and histology workflow

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