scholarly journals Localization of Free and Bound Metal Species through X-Ray Synchrotron Fluorescence Microscopy in the Rodent Brain and Their Relation to Behavior

2019 ◽  
Vol 9 (4) ◽  
pp. 74 ◽  
Author(s):  
Caroline Neely ◽  
Stephen Lippi ◽  
Antonio Lanzirotti ◽  
Jane Flinn
Keyword(s):  
Fluorescence Microscopy ◽  
Cell Signaling ◽  
Cell Types ◽  
Brain Regions ◽  
Metal Species ◽  
X Ray ◽  
Mediate Cell ◽  
And Behavior ◽  
Regulatory Functions ◽  
The Brain

Biometals in the brain, such as zinc, copper, and iron, are often discussed in cases of neurological disorders; however, these metals also have important regulatory functions and mediate cell signaling and plasticity. With the use of synchrotron X-ray fluorescence, our lab localized total, both bound and free, levels of zinc, copper, and iron in a cross section of one hemisphere of a rat brain, which also showed differing metal distributions in different regions within the hippocampus, the site in the brain known to be crucial for certain types of memory. This review discusses the several roles of these metals in brain regions with an emphasis on hippocampal cell signaling, based on spatial mapping obtained from X-ray fluorescence microscopy. We also discuss the localization of these metals and emphasize different cell types and receptors in regions with metal accumulation, as well as the potential relationship between this physiology and behavior.

scholarly journals Location Matters: Navigating Regional Heterogeneity of the Neurovascular Unit

2021 ◽  
Vol 15 ◽  
Author(s):  
Louis-Philippe Bernier ◽  
Clément Brunner ◽  
Azzurra Cottarelli ◽  
Matilde Balbi
Keyword(s):  
Brain Function ◽  
Energy Demand ◽  
Neurovascular Unit ◽  
Cell Types ◽  
Brain Regions ◽  
Regional Heterogeneity ◽  
Regional Specialization ◽  
Multiple Cell ◽  
Cellular Components ◽  
The Brain

The neurovascular unit (NVU) of the brain is composed of multiple cell types that act synergistically to modify blood flow to locally match the energy demand of neural activity, as well as to maintain the integrity of the blood-brain barrier (BBB). It is becoming increasingly recognized that the functional specialization, as well as the cellular composition of the NVU varies spatially. This heterogeneity is encountered as variations in vascular and perivascular cells along the arteriole-capillary-venule axis, as well as through differences in NVU composition throughout anatomical regions of the brain. Given the wide variations in metabolic demands between brain regions, especially those of gray vs. white matter, the spatial heterogeneity of the NVU is critical to brain function. Here we review recent evidence demonstrating regional specialization of the NVU between brain regions, by focusing on the heterogeneity of its individual cellular components and briefly discussing novel approaches to investigate NVU diversity.

scholarly journals STAB: a spatio-temporal cell atlas of the human brain

2020 ◽  
Vol 49 (D1) ◽  
pp. D1029-D1037
Author(s):  
Liting Song ◽  
Shaojun Pan ◽  
Zichao Zhang ◽  
Longhao Jia ◽  
Wei-Hua Chen ◽  
...  
Keyword(s):  
Human Brain ◽  
Single Cell ◽  
Temporal Dynamics ◽  
Cell Types ◽  
Brain Regions ◽  
Molecular Characteristics ◽  
Great Effort ◽  
Brain Functions ◽  
Spatio Temporal ◽  
The Brain

Abstract The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.

scholarly journals Glucocorticoid receptor action in metabolic and neuronal function

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1208 ◽  
Author(s):  
Michael J. Garabedian ◽  
Charles A. Harris ◽  
Freddy Jeanneteau
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Health And Disease ◽  
And Behavior ◽  
External Signals ◽  
The Brain

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.

scholarly journals Regulation and Modulation of pH in the Brain

2003 ◽  
Vol 83 (4) ◽  
pp. 1183-1221 ◽  
Author(s):  
MITCHELL CHESLER
Keyword(s):  
Intracellular Ph ◽  
Neural Activity ◽  
Extracellular Fluid ◽  
Cell Types ◽  
Brain Regions ◽  
Metabolic Products ◽  
Homeostatic Function ◽  
Acid Extrusion ◽  
Activity Dependent ◽  
The Brain

Chesler, Mitchell. Regulation and Modulation of pH in the Brain. Physiol Rev 83: 1183-1221, 2003; 10.1152/physrev.00010.2003.—The regulation of pH is a vital homeostatic function shared by all tissues. Mechanisms that govern H+ in the intracellular and extracellular fluid are especially important in the brain, because electrical activity can elicit rapid pH changes in both compartments. These acid-base transients may in turn influence neural activity by affecting a variety of ion channels. The mechanisms responsible for the regulation of intracellular pH in brain are similar to those of other tissues and are comprised principally of forms of Na+/H+ exchange, Na+-driven Cl-/HCO3- exchange, Na+-HCO3- cotransport, and passive Cl-/HCO3- exchange. Differences in the expression or efficacy of these mechanisms have been noted among the functionally and morphologically diverse neurons and glial cells that have been studied. Molecular identification of transporter isoforms has revealed heterogeneity among brain regions and cell types. Neural activity gives rise to an assortment of extracellular and intracellular pH shifts that originate from a variety of mechanisms. Intracellular pH shifts in neurons and glia have been linked to Ca2+ transport, activation of acid extrusion systems, and the accumulation of metabolic products. Extracellular pH shifts can occur within milliseconds of neural activity, arise from an assortment of mechanisms, and are governed by the activity of extracellular carbonic anhydrase. The functional significance of these compartmental, activity-dependent pH shifts is discussed.

scholarly journals Convergence Circuit Mapping: Genetic Approaches From Structure to Function

2021 ◽  
Vol 15 ◽  
Author(s):  
Jang Soo Yook ◽  
Jihyun Kim ◽  
Jinhyun Kim
Keyword(s):  
Fluorescent Proteins ◽  
Brain Activity ◽  
Molecular Genetic ◽  
Cell Types ◽  
Brain Regions ◽  
Genetically Engineered ◽  
Spatiotemporal Resolution ◽  
Genetic Switches ◽  
A Cell ◽  
And Behavior

Understanding the complex neural circuits that underpin brain function and behavior has been a long-standing goal of neuroscience. Yet this is no small feat considering the interconnectedness of neurons and other cell types, both within and across brain regions. In this review, we describe recent advances in mouse molecular genetic engineering that can be used to integrate information on brain activity and structure at regional, cellular, and subcellular levels. The convergence of structural inputs can be mapped throughout the brain in a cell type-specific manner by antero- and retrograde viral systems expressing various fluorescent proteins and genetic switches. Furthermore, neural activity can be manipulated using opto- and chemo-genetic tools to interrogate the functional significance of this input convergence. Monitoring neuronal activity is obtained with precise spatiotemporal resolution using genetically encoded sensors for calcium changes and specific neurotransmitters. Combining these genetically engineered mapping tools is a compelling approach for unraveling the structural and functional brain architecture of complex behaviors and malfunctioned states of neurological disorders.

scholarly journals MRI of Capn15 knockout mice and analysis of Capn15 distribution reveal possible roles in brain development and plasticity

2019 ◽  
Author(s):  
Congyao Zha ◽  
Carole A Farah ◽  
Vladimir Fonov ◽  
David A. Rudko ◽  
Wayne S Sossin
Keyword(s):  
Brain Development ◽  
Knockout Mice ◽  
Brain Plasticity ◽  
Small Animal ◽  
Cell Types ◽  
Cysteine Proteases ◽  
Brain Regions ◽  
Conditional Knockout ◽  
Specific Cell ◽  
The Brain

AbstractPurposeThe non-classical Small Optic Lobe (SOL) family of calpains are intracellular cysteine proteases that are expressed in the nervous system and appear to play an important role in neuronal development in both Drosophila, where loss of this calpain leads to the eponymous small optic lobes, and in mouse and human, where loss of this calpain (Capn15) leads to eye anomalies. However, the brain regions where this calpain is expressed and the areas most affected by the loss of this calpain have not been carefully examined.ProceduresWe utilize an insert strain where lacZ is expressed under the control of the Capn15 promoter, together with immunocytochemistry with markers of specific cell types to address where Capn 15 is expressed in the brain. We use small animal MRI comparing WT, Capn15 knockout and Capn15 conditional knockout mice to address the brain regions that are affected when Capn 15 is not present, either in early development of the adult.ResultsCapn15 is expressed in diverse brain regions, many of them involved in plasticity such as the hippocampus, lateral amygdala and Purkinje neurons. Capn15 knockout mice have smaller brains, and present specific deficits in the thalamus and hippocampal regions. There are no deficits revealed by MRI in brain regions when Capn15 is knocked out after development.ConclusionsAreas where Capn15 is expressed in the adult are not good markers for the specific regions where the loss of Capn15 specifically affects brain development. Thus, it is likely that this calpain plays distinct roles in brain development and brain plasticity.

scholarly journals A Connectome of the Adult Drosophila Central Brain

2020 ◽  
Author(s):  
C. Shan Xu ◽  
Michal Januszewski ◽  
Zhiyuan Lu ◽  
Shin-ya Takemura ◽  
Kenneth J. Hayworth ◽  
...  
Keyword(s):  
Large Fraction ◽  
Large Data ◽  
Fruit Fly ◽  
Cell Types ◽  
Brain Regions ◽  
Central Complex ◽  
Data Set ◽  
New Methods ◽  
Central Brain ◽  
The Brain

AbstractThe neural circuits responsible for behavior remain largely unknown. Previous efforts have reconstructed the complete circuits of small animals, with hundreds of neurons, and selected circuits for larger animals. Here we (the FlyEM project at Janelia and collaborators at Google) summarize new methods and present the complete circuitry of a large fraction of the brain of a much more complex animal, the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses, and proofread such large data sets; new methods that define cell types based on connectivity in addition to morphology; and new methods to simplify access to a large and evolving data set. From the resulting data we derive a better definition of computational compartments and their connections; an exhaustive atlas of cell examples and types, many of them novel; detailed circuits for most of the central brain; and exploration of the statistics and structure of different brain compartments, and the brain as a whole. We make the data public, with a web site and resources specifically designed to make it easy to explore, for all levels of expertise from the expert to the merely curious. The public availability of these data, and the simplified means to access it, dramatically reduces the effort needed to answer typical circuit questions, such as the identity of upstream and downstream neural partners, the circuitry of brain regions, and to link the neurons defined by our analysis with genetic reagents that can be used to study their functions.Note: In the next few weeks, we will release a series of papers with more involved discussions. One paper will detail the hemibrain reconstruction with more extensive analysis and interpretation made possible by this dense connectome. Another paper will explore the central complex, a brain region involved in navigation, motor control, and sleep. A final paper will present insights from the mushroom body, a center of multimodal associative learning in the fly brain.

The somatic error hypothesis of anxiety

2018 ◽  
Author(s):  
Sahib S. Khalsa ◽  
Justin S. Feinstein
Keyword(s):  
Central Nervous System ◽  
Physiological State ◽  
Brain Regions ◽  
Novel Therapies ◽  
Body State ◽  
Long Term Changes ◽  
The Central Nervous System ◽  
And Behavior ◽  
The Brain

A regulatory battle for control ensues in the central nervous system following a mismatch between the current physiological state of an organism as mapped in viscerosensory brain regions and the predicted body state as computed in visceromotor control regions. The discrepancy between the predicted and current body state (i.e. the “somatic error”) signals a need for corrective action, motivating changes in both cognition and behavior. This chapter argues that anxiety disorders are fundamentally driven by somatic errors that fail to be adaptively regulated, leaving the organism in a state of dissonance where the predicted body state is perpetually out of line with the current body state. Repeated failures to quell somatic error can result in long-term changes to interoceptive circuitry within the brain. This chapter explores the neuropsychiatric sequelae that can emerge following chronic allostatic dysregulation of somatic errors and discusses novel therapies that might help to correct this dysregulation.

scholarly journals A single-cell transcriptomic atlas of the adult Drosophila ventral nerve cord

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Aaron M Allen ◽  
Megan C Neville ◽  
Sebastian Birtles ◽  
Vincent Croset ◽  
Christoph Daniel Treiber ◽  
...  
Keyword(s):  
Single Cell ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Sensory Information ◽  
Neuronal Cell ◽  
Cell Types ◽  
Distinct Cell ◽  
Old Adult ◽  
And Behavior ◽  
The Brain

The Drosophila ventral nerve cord (VNC) receives and processes descending signals from the brain to produce a variety of coordinated locomotor outputs. It also integrates sensory information from the periphery and sends ascending signals to the brain. We used single-cell transcriptomics to generate an unbiased classification of cellular diversity in the VNC of five-day old adult flies. We produced an atlas of 26,000 high-quality cells, representing more than 100 transcriptionally distinct cell types. The predominant gene signatures defining neuronal cell types reflect shared developmental histories based on the neuroblast from which cells were derived, as well as their birth order. The relative position of cells along the anterior-posterior axis could also be assigned using adult Hox gene expression. This single-cell transcriptional atlas of the adult fly VNC will be a valuable resource for future studies of neurodevelopment and behavior.

scholarly journals Classification and genetic targeting of cell types in the primary taste and premotor center of the adult Drosophila brain

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Gabriella R Sterne ◽  
Hideo Otsuna ◽  
Barry J Dickson ◽  
Kristin Scott
Keyword(s):  
Sensory Processing ◽  
Cell Types ◽  
Brain Regions ◽  
Projection Neurons ◽  
Sensorimotor Transformations ◽  
Drosophila Brain ◽  
Genetic Targeting ◽  
And Behavior ◽  
Insight Into ◽  
Adult Drosophila

Neural circuits carry out complex computations that allow animals to evaluate food, select mates, move toward attractive stimuli, and move away from threats. In insects, the subesophageal zone (SEZ) is a brain region that receives gustatory, pheromonal, and mechanosensory inputs and contributes to the control of diverse behaviors, including feeding, grooming, and locomotion. Despite its importance in sensorimotor transformations, the study of SEZ circuits has been hindered by limited knowledge of the underlying diversity of SEZ neurons. Here, we generate a collection of split-GAL4 lines that provides precise genetic targeting of 138 different SEZ cell types in adult D. melanogaster, comprising approximately one third of all SEZ neurons. We characterize the single cell anatomy of these neurons and find that they cluster by morphology into six supergroups that organize the SEZ into discrete anatomical domains. We find that the majority of local SEZ interneurons are not classically polarized, suggesting rich local processing, whereas SEZ projection neurons tend to be classically polarized, conveying information to a limited number of higher brain regions. This study provides insight into the anatomical organization of the SEZ and generates resources that will facilitate further study of SEZ neurons and their contributions to sensory processing and behavior.

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