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.

Differential expression of glutamate receptor genes (GluR1-5) in the rat retina

1992 ◽  
Vol 8 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Thomas E. Hughes ◽  
Irm Hermans-Borgmeyer ◽  
Steve Heinemann
Keyword(s):  
Glutamate Receptor ◽  
Amacrine Cells ◽  
Cell Types ◽  
Bipolar Cells ◽  
Inner Nuclear Layer ◽  
Dissociated Cells ◽  
Different Cell Types ◽  
The Brain ◽  
Overlapping Sets

AbstractThe recent isolation of at least five different cDNAs encoding functional subunits of glutamate receptors (GluR1 to GluR5) has revealed a diversity whose function is not understood. To learn more about how these different receptor subunits are used in the brain, we undertook an in situ hybridization study of the retina to define how the different glutamate receptor genes are expressed. We chose the retina because the glutamate sensitivities of its different cell types have been characterized, and these different neurons reside in different laminae.Hybridization of [35S]UTP-labeled cRNA probes with transverse sections and freshly dissociated cells reveals that all five receptor subunits are expressed in the retina. Hybridization signal is detected in different, but overlapping, sets of cells in the retina. GluR1, GluR2, and GluR5 are expressed by many somata, and GluR4 by a few, in the outer third of the inner nuclear layer, where the horizontal cells reside. Transcripts for GluR1, GluR2, and GluR5 are found in the somata within the middle third of the inner nuclear layer, which is where the bipolar cell somata are located, and GluR2 probes label freshly dissociated rod bipolar cells. All of the probes produce labeling over the cells at the inner edge of the inner nuclear layer, which are probably amacrine cells, as well as over the cell bodies in the ganglion cell layer.

scholarly journals Neuronal expression of STM2 mRNA in human brain is reduced in Alzheimer's disease.

1996 ◽  
Vol 44 (11) ◽  
pp. 1215-1222 ◽  
Author(s):  
P J McMillan ◽  
J B Leverenz ◽  
P Poorkaj ◽  
G D Schellenberg ◽  
D M Dorsa
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Basal Forebrain ◽  
Cell Types ◽  
Hybridization Histochemistry ◽  
In Situ Hybridization Histochemistry ◽  
A Cell ◽  
The Brain

Mutations in the STM2 gene cause familial Alzheimer's disease (AD) in Volga Germans. To understand the function of this protein and how mutations lead to AD, it is important to determine which cell types in the brain express this gene. In situ hybridization histochemistry indicates that STM2 expression in the human brain is widespread and is primarily neuronal. In addition, STM2 mRNA is expressed in a cell line with neuronal origins. Quantification of the level of expression of the STM2 message in the basal forebrain, frontal cortex, and hippocampus reveals a significant decrease in AD-affected subjects compared to normal age-matched controls. These data suggest that downregulation of neuronal STM2 gene expression may be involved in the progression of AD.

scholarly journals Identification of KiSS-1 Product Kisspeptin and Steroid-Sensitive Sexually Dimorphic Kisspeptin Neurons in Medaka (Oryzias latipes)

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2467-2476 ◽  
Author(s):  
Shinji Kanda ◽  
Yasuhisa Akazome ◽  
Takuya Matsunaga ◽  
Naoyuki Yamamoto ◽  
Shunji Yamada ◽  
...  
Keyword(s):  
Mammalian Species ◽  
Sexually Dimorphic ◽  
Neuronal System ◽  
Anatomical Distribution ◽  
Neuronal Populations ◽  
Hypothalamic Nuclei ◽  
Steroid Sensitive ◽  
Neuronal Systems ◽  
The Brain

Recently, a novel physiologically active peptide, kisspeptin (metastin), has been reported to facilitate sexual maturation and ovulation by directly stimulating GnRH neurons in several mammalian species. Despite its importance in the neuroendocrine regulation of reproduction, kisspeptin neurons have only been studied in mammals, and there has been no report on the kisspeptin or kisspeptin neuronal systems in nonmammalian vertebrates. We used medaka for the initial identification of the KiSS-1 gene and the anatomical distribution of KiSS-1 mRNA expressing neurons (KiSS-1 neurons) in the brain of nonmammalian species. In situ hybridization for the medaka KiSS-1 gene cloned here proved that two kisspeptin neuronal populations are localized in the hypothalamic nuclei, the nucleus posterioris periventricularis and the nucleus ventral tuberis (NVT). Furthermore, NVT KiSS-1 neurons were sexually dimorphic in number (male neurons ≫ female neurons) under the breeding conditions. We also found that the number of KiSS-1 neurons in the NVT but not that in the nucleus posterioris periventricularis was positively regulated by ovarian estrogens. The fact that there were clear differences in the number of NVT KiSS-1 neurons between the fish under the breeding and nonbreeding conditions strongly suggests that the steroid-sensitive changes in the KiSS-1 mRNA expression in the NVT occur physiologically, according to the changes in the reproductive state. From the present results, we conclude that the medaka KiSS-1 neuronal system is involved in the central regulation of reproductive functions, and, given many experimental advantages, the medaka brain may serve as a good model system to study its physiology.

scholarly journals Tanycyte-independent control of hypothalamic leptin signaling

2019 ◽  
Author(s):  
Sooyeon Yoo ◽  
David Cha ◽  
Dong Won Kim ◽  
Thanh V. Hoang ◽  
Seth Blackshaw
Keyword(s):  
Gene Expression ◽  
Single Molecule ◽  
Leptin Receptor ◽  
Cell Types ◽  
Leptin Signaling ◽  
And Function ◽  
Induced Changes ◽  
The Brain ◽  
Specific Deletion

AbstractLeptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms.

scholarly journals Spatial organization of the somatosensory cortex revealed by cyclic smFISH

2018 ◽  
Author(s):  
Simone Codeluppi ◽  
Lars E. Borm ◽  
Amit Zeisel ◽  
Gioele La Manno ◽  
Josina A. van Lunteren ◽  
...  
Keyword(s):  
Single Cell ◽  
Somatosensory Cortex ◽  
Single Molecule ◽  
Spatial Organization ◽  
Spatial Information ◽  
Cell Types ◽  
Cellular Organization ◽  
New Methods ◽  
The Brain

The global efforts towards the creation of a molecular census of the brain using single-cell transcriptomics is generating a large catalog of molecularly defined cell types lacking spatial information. Thus, new methods are needed to map a large number of cell-specific markers simultaneously on large tissue areas. Here, we developed a cyclic single molecule fluorescence in situ hybridization methodology and defined the cellular organization of the somatosensory cortex using markers identified by single-cell transcriptomics.

scholarly journals Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics

2017 ◽  
Author(s):  
Vincent Croset ◽  
Christoph D Treiber ◽  
Scott Waddell
Keyword(s):  
Single Cell ◽  
Neural Circuit ◽  
Cell Types ◽  
Brain Regions ◽  
Neurotransmitter Receptor ◽  
Neural Processes ◽  
Subunit Expression ◽  
Circuit Function ◽  
Fast Acting ◽  
The Brain

AbstractTo understand the brain, molecular details need to be overlaid onto neural wiring diagrams so that synaptic mode, neuromodulation and critical signaling operations can be considered. Single-cell transcriptomics provide a unique opportunity to collect this information. Here we present an initial analysis of thousands of individual cells from Drosophila midbrain, that were acquired using Drop-Seq. A number of approaches permitted the assignment of transcriptional profiles to several major brain regions and cell-types. Expression of biosynthetic enzymes and reuptake mechanisms allows all the neurons to be typed according to the neurotransmitter or neuromodulator that they produce and presumably release. Some neuropeptides are preferentially co-expressed in neurons using a particular fast-acting transmitter, or monoamine. Neuromodulatory and neurotransmitter receptor subunit expression illustrates the potential of these molecules in generating complexity in neural circuit function. This cell atlas dataset provides an important resource to link molecular operations to brain regions and complex neural processes.

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.

scholarly journals An operant temperature sensory assay provides a means to assess thermal discrimination

2021 ◽  
Vol 17 ◽  
pp. 174480692110136
Author(s):  
Matthew Isaacson ◽  
Mark A Hoon
Keyword(s):  
Temperature Change ◽  
Behavioral Responses ◽  
Large Temperature ◽  
Thermal Nociception ◽  
Temperature Changes ◽  
Neuronal Populations ◽  
Rapid Temperature ◽  
Thermal Stimuli ◽  
The Brain ◽  
Behavioral Assays

Mouse behavioral assays have proven useful for the study of thermosensation, helping to identify receptors and circuits responsible for the transduction of thermal stimuli and information relay to the brain. However, these methods typically rely on observation of behavioral responses to various temperature stimuli to infer sensory ability and are often unable to disambiguate innocuous thermosensation from thermal nociception or to study thermosensory circuitry which do not produce easily detectable innate behavioral responses. Here we demonstrate a new testing apparatus capable of delivering small, rapid temperature change stimuli to the mouse’s skin, permitting the use of operant conditioning to train mice to recognize and report temperature change. Using this assay, mice that were trained to detect a large temperature change were found to generalize this learning to distinguish much smaller temperature changes across the entire range of innocuous temperatures tested. Mice with ablated TRPV1 and TRPM8 neuronal populations had reduced ability to discriminate temperature differences in the warm (>35°C) and cool (<30°C) ranges, respectively. Furthermore, mice that were trained to recognize temperature changes in only the cool, TRPM8-mediated temperature range did not generalize this learning in the warm, TRPV1-mediated range (and vice versa), suggesting that thermosensory information from the TRPM8- and TRPV1-neuronal populations are perceptually distinct.

scholarly journals Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Vincent Croset ◽  
Christoph D Treiber ◽  
Scott Waddell
Keyword(s):  
Single Cell ◽  
Neural Circuit ◽  
Cell Types ◽  
Brain Regions ◽  
Neurotransmitter Receptor ◽  
Neural Processes ◽  
Subunit Expression ◽  
Circuit Function ◽  
Fast Acting ◽  
The Brain

To understand the brain, molecular details need to be overlaid onto neural wiring diagrams so that synaptic mode, neuromodulation and critical signaling operations can be considered. Single-cell transcriptomics provide a unique opportunity to collect this information. Here we present an initial analysis of thousands of individual cells from Drosophila midbrain, that were acquired using Drop-Seq. A number of approaches permitted the assignment of transcriptional profiles to several major brain regions and cell-types. Expression of biosynthetic enzymes and reuptake mechanisms allows all the neurons to be typed according to the neurotransmitter or neuromodulator that they produce and presumably release. Some neuropeptides are preferentially co-expressed in neurons using a particular fast-acting transmitter, or monoamine. Neuromodulatory and neurotransmitter receptor subunit expression illustrates the potential of these molecules in generating complexity in neural circuit function. This cell atlas dataset provides an important resource to link molecular operations to brain regions and complex neural processes.

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