Optogenetic and chemogenetic technologies for advanced functional investigations of the neural correlates of emotions

2019 ◽  
pp. 97-110
Author(s):  
Alexandre Surget ◽  
Catherine Belzung
Keyword(s):  
Human Subjects ◽  
Specific Area ◽  
Cell Types ◽  
Brain Lesions ◽  
Causal Relations ◽  
Neuronal Populations ◽  
Time Period ◽  
Distinct Cell ◽  
The Brain

The neural circuits underlying emotions have been extensively examined in the last decades, using either correlational approaches (e.g. functional imaging in human subjects or post-mortem immunohistochemistry in rodents) or methodologies enabling to investigate causal relationships (such as focused brain lesions in animals). However, each of these approaches has strong limitations that have hampered research in this field. The first approaches do not enable investigation of causal relations; they allow determining associations of particular emotional expressions with distinct cell populations or brain areas. The second approach enables the determination of causal relations but not the inhibition of particular cell types or projections or the investigation of the effects of manipulating neuronal activity during a restricted time period. Optogenetic and chemogenetic approaches are two cutting-edge methodologies that enabled ground-breaking research in the field of emotion in recent years. These approaches make possible the stimulation or inhibition of specific neuronal populations/projections in a specific area of the brain, during a precise period of time, thus permitting the dissection of the contribution of precise neuronal populations, sub-areas, and outputs to the different components of emotions. It is strongly impacting research in this field, providing a more complex and rich view of the biology of normal emotions.

Thoughts for the Future

2020 ◽  
pp. 497-508
Author(s):  
Richard McCarty
Keyword(s):  
Mental Disorders ◽  
Specific Area ◽  
Neuronal Cultures ◽  
Common Theme ◽  
Use Of Data ◽  
The Future ◽  
Induced Pluripotent ◽  
The Brain

Several exciting lines of research have emerged from the study of animal models of mental disorders. This chapter presents seven opportunities for enhancing the diagnosis and treatment of mental disorders. They include improvements to the system for diagnosis of mental disorders, use of induced pluripotent stem cells from patients to generate neuronal cultures for in vitro determination of effective drug therapies for those individuals, use of data-mining techniques for understanding patient variability, a commitment to a greater focus on the prevention of mental disorders, innovative uses of smartphones to track patients and individuals at high risk of developing a mental disorder, and developing next-generation therapies and delivery systems that target a specific area of the brain rather than the entire brain. A common theme in these seven thoughts for the future is a commitment to bringing precision medicine tools to the treatment of patients with mental disorders.

scholarly journals Material and Structural Modeling Aspects of Brain Tissue Deformation under Dynamic Loads

Materials ◽  
2019 ◽  
Vol 12 (2) ◽  
pp. 271 ◽  
Author(s):  
Monika Ratajczak ◽  
Mariusz Ptak ◽  
Leszek Chybowski ◽  
Katarzyna Gawdzińska ◽  
Romuald Będziński
Keyword(s):  
Brain Tissue ◽  
Human Subjects ◽  
Experimental Studies ◽  
Material Modeling ◽  
Geometrical Parameters ◽  
Dynamic Loading Conditions ◽  
Technological Improvements ◽  
The Impact ◽  
The Brain

The aim of this work was to assess the numerous approaches to structural and material modeling of brain tissue under dynamic loading conditions. The current technological improvements in material modeling have led to various approaches described in the literature. However, the methods used for the determination of the brain’s characteristics have not always been stated or clearly defined and material data are even more scattered. Thus, the research described in this paper explicitly underlines directions for the development of numerical brain models. An important element of this research is the development of a numerical model of the brain based on medical imaging methods. This approach allowed the authors to assess the changes in the mechanical and geometrical parameters of brain tissue caused by the impact of mechanical loads. The developed model was verified through comparison with experimental studies on post-mortem human subjects described in the literature, as well as through numerical tests. Based on the current research, the authors identified important aspects of the modeling of brain tissue that influence the assessment of the actual biomechanical response of the brain for dynamic analyses.

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 Cellular taxonomy and spatial organization of the ventral posterior hypothalamus reveals neuroanatomical parcellation of the mammillary bodies

2020 ◽  
Author(s):  
Laura E. Mickelsen ◽  
William F. Flynn ◽  
Kristen Springer ◽  
Lydia Wilson ◽  
Eric J. Beltrami ◽  
...  
Keyword(s):  
Single Cell ◽  
Spatial Organization ◽  
Single Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Posterior Hypothalamus ◽  
Neuronal Populations ◽  
Mammillary Bodies ◽  
Distinct Cell ◽  
And Behavior

ABSTRACTThe ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell types in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in a selection of neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit a surprising degree of segregation within neuroanatomical subdivisions of the MB, while genetically-defined MB cell types project topographically to the anterior thalamus. This single cell transcriptomic atlas of cell types in the VPH provides a detailed resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits in health and disease.

Mechanisms of glycolysis and bioenergy state of cells at the stages of cardiosurgical interventions in patients with hypoxic — ischemic impairments of the brain

2021 ◽  
Author(s):  
D. S. Mankovsky
Keyword(s):  
Cardiac Surgery ◽  
Energy Homeostasis ◽  
Brain Lesions ◽  
Artificial Circulation ◽  
Ischemic Brain ◽  
Bioenergetic Metabolism ◽  
Before And After ◽  
The Brain ◽  
Oxidative Homeostasis

Objective — to study the features of bioenergetic provision of oxidative homeostasis (OH) in patients with hypoxic‑ischemic brain lesions (HIBL) before and after cardiac surgery (CS) using artificial circulation (AC). Methods and subjects. Clinical and biochemical studies were performed in 38 patients, including 14 with ischemic stroke, 15 with encephalopathy, and 9 with severe cognitive dysfunction. Results. Analysis of metabolic indicators of glycolysis activity and energy homeostasis of cells before and after CS revealed the patterns of changes in the disorganization of glycolysis mechanisms, intensification of anaerobic mechanisms while limiting the energy supply of cells. The obtained data confirm the formation of specific postoperative metabolic provision of bioenergy in patients with CS, which should be considered as one of the triggers of HIBL and individualization of antioxidant cerebroprotection in the preoperative period, taking into account the state of bioenergetic metabolism of cells and the dominant mechanisms of glycolysis. Conclusions. Preoperative antioxidant cerebroprotection as a means of prevention of hypoxic‑ischemic brain lesions during cardiac surgery using artificial circulation should be based on the determination of bioenergetic and metabolic reserves, the depletion of which by antioxidant drugs suppression should not be considered, as activation of anaerobic glycolysis at simultaneous metabolic suppression of mitochondrial bioenergetics is a factor of formation or aggravation of ischemic lesions of brain.  

scholarly journals Delayed-matching-to-position working memory in mice relies on NMDA-receptors in prefrontal pyramidal cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kasyoka Kilonzo ◽  
Bastiaan van der Veen ◽  
Jasper Teutsch ◽  
Stefanie Schulz ◽  
Sampath K. T. Kapanaiah ◽  
...  
Keyword(s):  
Working Memory ◽  
Pyramidal Cells ◽  
Cell Types ◽  
Delayed Matching ◽  
Hedonic Valuation ◽  
Distinct Cell ◽  
Excitatory Neurons ◽  
Processing Motivation ◽  
The Brain ◽  
Matching To Position

AbstractA hypofunction of N-methyl-D-aspartate glutamate receptors (NMDARs) has been implicated in the pathogenesis of schizophrenia by clinical and rodent studies. However, to what extent NMDAR-hypofunction in distinct cell-types across the brain causes different symptoms of this disease is largely unknown. One pharmaco-resistant core symptom of schizophrenia is impaired working memory (WM). NMDARs have been suggested to mediate sustained firing in excitatory neurons of the prefrontal cortex (PFC) that might underlie WM storage. However, if NMDAR-hypofunction in prefrontal excitatory neurons may indeed entail WM impairments is unknown. We here investigated this question in mice, in which NMDARs were genetically-ablated in PFC excitatory cells. This cell type-selective NMDAR-hypofunction caused a specific deficit in a delayed-matching-to-position (DMTP) 5-choice-based operant WM task. In contrast, T-maze rewarded alternation and several psychological functions including attention, spatial short-term habituation, novelty-processing, motivation, sociability, impulsivity, and hedonic valuation remained unimpaired at the level of GluN1-hypofunction caused by our manipulation. Our data suggest that a hypofunction of NMDARs in prefrontal excitatory neurons may indeed cause WM impairments, but are possibly not accounting for most other deficits in schizophrenia.

scholarly journals Peptidergic modulation of fear responses by the Edinger-Westphal nucleus

2021 ◽  
Author(s):  
Michael F Priest ◽  
Sara N Freda ◽  
Deanna Badong ◽  
Vasin Dumrongprechachan ◽  
Yevgenia Kozorovitskiy
Keyword(s):  
Cell Types ◽  
Projection Mapping ◽  
Inhibitory Neurotransmitters ◽  
Neuronal Populations ◽  
Electrophysiological Characterization ◽  
Fast Acting ◽  
The Brain ◽  
Behavioral Assays ◽  
Edinger Westphal Nucleus

Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether obligate peptidergic neurons exist. Our fluorescence in situ hybridization, genetically-targeted electron microscopy, and electrophysiological characterization data strongly suggest that neurons of the non-cholinergic, centrally-projecting Edinger-Westphal nucleus in mice are fundamentally obligately peptidergic. We further show, using fiber photometry, monosynaptic retrograde tracing, anterograde projection mapping, and a battery of behavioral assays, that this peptidergic population both promotes fear responses and analgesia and activates in response to loss of motor control and pain. Together, these findings elucidate an integrative, ethologically relevant function for the Edinger-Westphal nucleus and functionally align the nucleus with the periaqueductal gray, where it resides. This work advances our understanding of the peptidergic modulation of fear and provides a framework for future investigations of putative obligate peptidergic systems.

scholarly journals Brain is an endocrine organ through secretion and nuclear transfer of parathymosin

2020 ◽  
Vol 3 (12) ◽  
pp. e202000917
Author(s):  
Bin Yu ◽  
Yizhe Tang ◽  
Dongsheng Cai
Keyword(s):  
Nuclear Transfer ◽  
Cell Types ◽  
Brain Regions ◽  
Long Distance ◽  
Endocrine Organ ◽  
Neuronal Nuclei ◽  
Neuronal Populations ◽  
Peripheral Cells ◽  
The Brain

This study reports that parathymosin (PTMS) is secreted by hypothalamic stem/progenitor cells (htNSC) to inhibit senescence of recipient cells such as fibroblasts. Upon release, PTMS is rapidly transferred into the nuclei of various cell types, including neuronal GT1-7 cells and different peripheral cells, and it is effectively transferred into neuronal nuclei in various brain regions in vivo. Notably, brain neurons also produce and release PTMS, and because neuronal populations are large, they are important for maintaining PTMS in the cerebrospinal fluid which is further transferable into the blood. Compared with several other brain regions, the hypothalamus is stronger for long-distance PTMS transfer, supporting a key hypothalamic role in this function. In physiology, aging is associated with declines in PTMS production and transfer in the brain, and ptms knockdown in the hypothalamus versus hippocampus were studied showing different contributions to neurobehavioral physiology. In conclusion, the brain is an endocrine organ through secretion and nuclear transfer of PTMS, and the hypothalamus–brain orchestration of this function is protective in physiology and counteractive against aging-related disorders.

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

2019 ◽  
Author(s):  
Aaron M. Allen ◽  
Megan C. Neville ◽  
Sebastian Birtles ◽  
Vincent Croset ◽  
Christoph D. Treiber ◽  
...  
Keyword(s):  
Single Cell ◽  
Nerve Cord ◽  
Ventral Nerve Cord ◽  
Sensory Information ◽  
Neuronal Cell ◽  
Cell Types ◽  
Distinct Cell ◽  
Old Adult ◽  
And Behavior ◽  
The Brain

AbstractThe 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. Cells could also be assigned to specific neuromeres 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 Cellular taxonomy and spatial organization of the murine ventral posterior hypothalamus

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Laura E Mickelsen ◽  
William F Flynn ◽  
Kristen Springer ◽  
Lydia Wilson ◽  
Eric J Beltrami ◽  
...  
Keyword(s):  
Single Cell ◽  
Spatial Organization ◽  
Single Cells ◽  
Neuronal Cell ◽  
Cell Types ◽  
Posterior Hypothalamus ◽  
Cell Populations ◽  
Neuronal Populations ◽  
Distinct Cell ◽  
And Behavior

The ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance, and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single-cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell populations in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in selected neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit neuroanatomical parcellation within MB subdivisions and topographic projections to the thalamus. This single-cell transcriptomic atlas of VPH cell types provides a resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits.

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