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 Brain Activity in Self- and Value-Related Regions in Response to Online Antismoking Messages Predicts Behavior Change

2015 ◽  
Vol 27 (3) ◽  
pp. 93-109 ◽  
Author(s):  
Nicole Cooper ◽  
Steve Tompson ◽  
Matthew Brook O’Donnell ◽  
B. Falk Emily
Keyword(s):  
Behavior Change ◽  
Risk Perceptions ◽  
Brain Activity ◽  
Smoking Behavior ◽  
Mechanistic Explanation ◽  
Health Behavior Change ◽  
Brain Regions ◽  
Self Report ◽  
Traditional Theory ◽  
And Behavior

Abstract. In this study, we combined approaches from media psychology and neuroscience to ask whether brain activity in response to online antismoking messages can predict smoking behavior change. In particular, we examined activity in subregions of the medial prefrontal cortex linked to self- and value-related processing, to test whether these neurocognitive processes play a role in message-consistent behavior change. We observed significant relationships between activity in both brain regions of interest and behavior change (such that higher activity predicted a larger reduction in smoking). Furthermore, activity in these brain regions predicted variance independent of traditional, theory-driven self-report metrics such as intention, self-efficacy, and risk perceptions. We propose that valuation is an additional cognitive process that should be investigated further as we search for a mechanistic explanation of the relationship between brain activity and media effects relevant to health behavior change.

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 Slc1a3-2A-CreERT2 mice reveal unique features of Bergmann glia and augment a growing collection of Cre drivers and effectors in the 129S4 genetic background

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lech Kaczmarczyk ◽  
Nicole Reichenbach ◽  
Nelli Blank ◽  
Maria Jonson ◽  
Lars Dittrich ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Phenotypic Diversity ◽  
Expression Patterns ◽  
Cell Types ◽  
Inbred Strains ◽  
Brain Regions ◽  
Genetically Engineered ◽  
Disease Models ◽  
Calcium Indicator ◽  
High Consistency

AbstractGenetic variation is a primary determinant of phenotypic diversity. In laboratory mice, genetic variation can be a serious experimental confounder, and thus minimized through inbreeding. However, generalizations of results obtained with inbred strains must be made with caution, especially when working with complex phenotypes and disease models. Here we compared behavioral characteristics of C57Bl/6—the strain most widely used in biomedical research—with those of 129S4. In contrast to 129S4, C57Bl/6 demonstrated high within-strain and intra-litter behavioral hyperactivity. Although high consistency would be advantageous, the majority of disease models and transgenic tools are in C57Bl/6. We recently established six Cre driver lines and two Cre effector lines in 129S4. To augment this collection, we genetically engineered a Cre line to study astrocytes in 129S4. It was validated with two Cre effector lines: calcium indicator gCaMP5g-tdTomato and RiboTag—a tool widely used to study cell type-specific translatomes. These reporters are in different genomic loci, and in both the Cre was functional and astrocyte-specific. We found that calcium signals lasted longer and had a higher amplitude in cortical compared to hippocampal astrocytes, genes linked to a single neurodegenerative disease have highly divergent expression patterns, and that ribosome proteins are non-uniformly expressed across brain regions and cell types.

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.

scholarly journals Insights into calcium signaling and gene expression in astrocytes uncovered with 129S4 Slc1a3-2A-CreERT2 knock-in mice

2020 ◽  
Author(s):  
Lech Kaczmarczyk ◽  
Nicole Reichenbach ◽  
Nelli Blank ◽  
Maria Jonson ◽  
Lars Dittrich ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Phenotypic Diversity ◽  
Expression Patterns ◽  
Cell Types ◽  
Inbred Strains ◽  
Brain Regions ◽  
Genetically Engineered ◽  
Calcium Currents ◽  
Activity Levels ◽  
Genomic Locus

AbstractGenetic variation is a primary determinant of phenotypic diversity within populations. In laboratory mice, genetic variation has often been regarded as a serious experimental confounder, and thus minimized through inbreeding. However, generalizations of results obtained with inbred strains need to be made with caution. Effects of genetic background on traits need to be controlled, especially when working with complex phenotypes and disease models. Here we compared behavioral parameters of C57Bl/6 – the mouse strain most widely used for biomedical research - with those of 129S4. Our data demonstrate high within-strain and intra-litter behavioral hyperactivity in C57Bl/6. In contrast, 129S4 had relatively consistent activity levels throughout life. This consistency would be advantageous for studying neurodegeneration and aging, when mice need to be analyzed for long periods. However, the majority of mouse models and transgenic tools are on a C57Bl/6 background. We recently established six popular Cre driver lines and two Cre effector lines in 129S4. To augment this collection, we genetically engineered a Cre mouse line to study astrocytes directly in 129S4, which we describe here. For functional validation, it was crossed with two Cre effector lines, each in a different genomic locus, and showed in both cases that it was functional and astrocyte-specific. Calcium currents studied with gCaMP5g-tdTomato were more heterogenous, lasted longer and had a higher amplitude in cortical compared to hippocampal astrocytes. Translatomes studied with RiboTag revealed that some genes thought to mark neurons are also expressed in astrocytes, that genes linked to a single neurodegenerative disease have highly divergent expression patterns, and that ribosome proteins are non-uniformly expressed across brain regions and cell types.

scholarly journals Physiological Functions of Mcl-1: Insights From Genetic Mouse Models

2021 ◽  
Vol 9 ◽  
Author(s):  
Hui San Chin ◽  
Nai Yang Fu
Keyword(s):  
Mouse Models ◽  
Developmental Stages ◽  
Cell Types ◽  
Genetically Engineered ◽  
Model Systems ◽  
Murine Models ◽  
Multiple Tumor ◽  
A Cell ◽  
Tumor Types

The ability to regulate the survival and death of a cell is paramount throughout the lifespan of a multicellular organism. Apoptosis, a main physiological form of programmed cell death, is regulated by the Bcl-2 family proteins that are either pro-apoptotic or pro-survival. The in vivo functions of distinct Bcl-2 family members are largely unmasked by genetically engineered murine models. Mcl-1 is one of the two Bcl-2 like pro-survival genes whose germline deletion causes embryonic lethality in mice. Its requisite for the survival of a broad range of cell types has been further unraveled by using conditional and inducible deletion murine model systems in different tissues or cell lineages and at distinct developmental stages. Moreover, genetic mouse cancer models have also demonstrated that Mcl-1 is essential for the survival of multiple tumor types. The MCL-1 locus is commonly amplified across various cancer types in humans. Small molecule inhibitors with high affinity and specificity to human MCL-1 have been developed and explored for the treatment of certain cancers. To facilitate the pre-clinical studies of MCL-1 in cancer and other diseases, transgenic mouse models over-expressing human MCL-1 as well as humanized MCL-1 mouse models have been recently engineered. This review discusses the current advances in understanding the physiological roles of Mcl-1 based on studies using genetic murine models and its critical implications in pathology and treatment of human diseases.

scholarly journals Individual Differences in Brain Responses: New Opportunities for Tailoring Health Communication Campaigns

2020 ◽  
Vol 14 ◽  
Author(s):  
Richard Huskey ◽  
Benjamin O. Turner ◽  
René Weber
Keyword(s):  
Individual Differences ◽  
Brain Activity ◽  
Brain Regions ◽  
Future Research ◽  
Message Processing ◽  
Response Patterns ◽  
Message Tailoring ◽  
Brain Responses ◽  
And Behavior ◽  
The Brain

Prevention neuroscience investigates the brain basis of attitude and behavior change. Over the years, an increasingly structurally and functionally resolved “persuasion network” has emerged. However, current studies have only identified a small handful of neural structures that are commonly recruited during persuasive message processing, and the extent to which these (and other) structures are sensitive to numerous individual difference factors remains largely unknown. In this project we apply a multi-dimensional similarity-based individual differences analysis to explore which individual factors—including characteristics of messages and target audiences—drive patterns of brain activity to be more or less similar across individuals encountering the same anti-drug public service announcements (PSAs). We demonstrate that several ensembles of brain regions show response patterns that are driven by a variety of unique factors. These results are discussed in terms of their implications for neural models of persuasion, prevention neuroscience and message tailoring, and methodological implications for future research.

scholarly journals fMRI and Transcranial Electrical Stimulation (tES): A systematic review of parameter space and outcomes

2020 ◽  
Author(s):  
Peyman Ghobadi-Azbari ◽  
Asif Jamil ◽  
Fatemeh Yavari ◽  
Zeinab Esmaeilpour ◽  
Nastaran Malmir ◽  
...  
Keyword(s):  
Systematic Review ◽  
Electrical Stimulation ◽  
Parameter Space ◽  
Brain Activity ◽  
Random Noise ◽  
Brain Regions ◽  
Transcranial Electrical Stimulation ◽  
Future Studies ◽  
Non Invasive ◽  
And Behavior

AbstractThe combination of non-invasive brain stimulation interventions with human brain mapping methods have supported research beyond correlational associations between brain activity and behavior. Functional MRI (fMRI) partnered with transcranial electrical stimulation (tES) methods, i.e., transcranial direct current (tDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation, explore the neuromodulatory effects of tES in the targeted brain regions and their interconnected networks and provide opportunities for individualized interventions. Advances in the field of tES-fMRI can be hampered by the methodological variability between studies that confounds comparability/replicability. In order to explore variability in the tES-fMRI methodological parameter space (MPS), we conducted a systematic review of 222 tES-fMRI experiments (181 tDCS, 39 tACS and 2 tRNS) published before February 1, 2019, and suggested a framework to systematically report main elements of MPS across studies. We have organized main findings in terms of fMRI modulation by tES. tES modulates activation and connectivity beyond the stimulated areas particularly with prefrontal stimulation. There were no two studies with the same MPS to replicate findings. We discuss how to harmonize the MPS to promote replication in future studies.

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

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

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.

scholarly journals Single-cell transcriptomics and cell-specific proteomics reveals molecular signatures of sleep

2020 ◽  
Author(s):  
Pawan K. Jha ◽  
Utham K. Valekunja ◽  
Sandipan Ray ◽  
Mathieu Nollet ◽  
Akhilesh B. Reddy
Keyword(s):  
Single Cell ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Brain Regions ◽  
Specific Protein ◽  
Cell Type ◽  
Transcriptional Responses ◽  
A Cell ◽  
Cell Type Specific ◽  
Different Cell Types

Every day, we sleep for a third of the day. Sleep is important for cognition, brain waste clearance, metabolism, and immune responses. The molecular mechanisms governing sleep are largely unknown. Here, we used a combination of single cell RNA sequencing and cell-type specific proteomics to interrogate the molecular underpinnings of sleep. Different cell types in three important brain regions for sleep (brainstem, cortex, and hypothalamus) exhibited diverse transcriptional responses to sleep need. Sleep restriction modulates astrocyte-neuron crosstalk and sleep need enhances expression of specific sets of transcription factors in different brain regions. In cortex, we also interrogated the proteome of two major cell types: astrocytes and neurons. Sleep deprivation differentially alters the expression of proteins in astrocytes and neurons. Similarly, phosphoproteomics revealed large shifts in cell-type specific protein phosphorylation. Our results indicate that sleep need regulates transcriptional, translational, and post-translational responses in a cell-specific manner.

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