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41. The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation Full Text available with Trip Pro

The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation The development of midbrain dopaminergic (mDA) neurons is controlled by multiple morphogens and transcription factors. However, little is known about the role of extracellular matrix proteins in this process. Here we examined the function of roof plate-specific spondins (RSPO1-4) and the floor plate-specific, spondin 1 (SPON1). Only RSPO2 and SPON1 were expressed at high levels during mDA (...) neurogenesis, and the receptor LGR5 was expressed by midbrain floor plate progenitors. Surprisingly, RSPO2, but not SPON1, specifically promoted the differentiation of mDA neuroblasts into mDA neurons in mouse primary cultures and embryonic stem cells (ESCs). In addition, RSPO2 was found to promote not only mDA differentiation, but also mDA neurogenesis in human ESCs. Our results thus uncover an unexpected function of the matricellular protein RSPO2 and suggest an application to improve mDA neurogenesis

2018 Stem cell reports

42. Anatomical Templates of the Midbrain Ventral Tegmental Area and Substantia Nigra for Asian Populations Full Text available with Trip Pro

Anatomical Templates of the Midbrain Ventral Tegmental Area and Substantia Nigra for Asian Populations Increasing evidence shows that the midbrain dopaminergic system is involved in various functions. However, details of the role of the midbrain dopaminergic system in these functions are still to be determined in humans. Considering that the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain are the primary dopamine producers, creating reliable anatomical templates (...) seeds that were created based on normalized templates from dataset 1. Subsequently, a seed-based functional connectivity analysis was performed using VTA and SN seeds in another, larger sample (dataset 2) to assess whether neural networks of VTA or SN seeds from dataset 1 would be replicated in dataset 2. The Asian VTA template was smaller and located in a more posterior and inferior part of the midbrain compared to the published VTA template, while the Asian SN template, relative to the published

2018 Frontiers in Psychiatry

43. Direct Glutamatergic Signaling From Midbrain Dopaminergic Neurons Onto Pyramidal Prefrontal Cortex Neurons Full Text available with Trip Pro

Direct Glutamatergic Signaling From Midbrain Dopaminergic Neurons Onto Pyramidal Prefrontal Cortex Neurons The dopaminergic neurons of the ventral tegmental area (VTA) have been identified with the ability to co-release dopamine and glutamate. This ability was first documented in the nucleus accumbens but showed to be absent in the dorsal striatum. Recently the ability to release glutamate from a subpopulation of the VTA dopaminergic neurons has been shown to control the prefrontal cortex (PFC

2018 Frontiers in neural circuits

44. Correction: Altered activation and connectivity in a hippocampal–basal ganglia–midbrain circuit during salience processing in subjects at ultra high risk for psychosis Full Text available with Trip Pro

Correction: Altered activation and connectivity in a hippocampal–basal ganglia–midbrain circuit during salience processing in subjects at ultra high risk for psychosis This Article was originally published under Nature Research's License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.

2018 Translational psychiatry

45. Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors Full Text available with Trip Pro

Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors Dopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet the temporal dynamic range and mechanism of action of acetylcholine (ACh) on the modulation of VTA circuits and reward-related behaviors are not known. Here, we used a chemical-genetic approach for rapid

2018 eLife

46. Transcriptomic analysis of left-right differences in human embryonic forebrain and midbrain Full Text available with Trip Pro

Transcriptomic analysis of left-right differences in human embryonic forebrain and midbrain Left-right asymmetry is subtle but pervasive in the human central nervous system. This asymmetry is initiated early during development, but its mechanisms are poorly known. Forebrains and midbrains were dissected from six human embryos at Carnegie stages 15 or 16, one of which was female. The structures were divided into left and right sides, and RNA was isolated. RNA was sequenced with 100 base-pair (...) paired ends using Illumina Hiseq 4000. After quality control, five paired brain sides were available for midbrain and forebrain. A paired analysis between left- and right sides of a given brain structure across the embryos identified left-right differences. The dataset, consisting of Fastq files and a read count table, can be further used to study early development of the human brain.

2018 Scientific data

47. Activation of the P2X7 receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats Full Text available with Trip Pro

Activation of the P2X7 receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats Background Cancer pain is a well-known serious complication in metastatic or terminal cancer patients. Current pain management remains unsatisfactory. The activation of spinal and supraspinal P2X7 receptors plays a crucial role in the induction and maintenance mechanisms of various kinds of acute or chronic pain. The midbrain periaqueductal gray is a vital

2018 Molecular pain

48. Neurotransmitter identity and electrophysiological phenotype are genetically coupled in midbrain dopaminergic neurons Full Text available with Trip Pro

Neurotransmitter identity and electrophysiological phenotype are genetically coupled in midbrain dopaminergic neurons Most neuronal types have a well-identified electrical phenotype. It is now admitted that a same phenotype can be produced using multiple biophysical solutions defined by ion channel expression levels. This argues that systems-level approaches are necessary to understand electrical phenotype genesis and stability. Midbrain dopaminergic (DA) neurons, although quite heterogeneous (...) , exhibit a characteristic electrical phenotype. However, the quantitative genetic principles underlying this conserved phenotype remain unknown. Here we investigated the quantitative relationships between ion channels' gene expression levels in midbrain DA neurons using single-cell microfluidic qPCR. Using multivariate mutual information analysis to decipher high-dimensional statistical dependences, we unravel co-varying gene modules that link neurotransmitter identity and electrical phenotype. We also

2018 Scientific reports

49. Cortical visual processing evokes short-latency reward-predicting cue responses in primate midbrain dopamine neurons Full Text available with Trip Pro

Cortical visual processing evokes short-latency reward-predicting cue responses in primate midbrain dopamine neurons After classical conditioning dopamine (DA) neurons exhibit short latency responses to reward-predicting visual cues. At least two possible projections could induce such DA responses; the cortical and subcortical visual pathways. Our recent study has shown that after a lesion of the striate cortex (V1), the superior colliculus (SC), a critical node of the subcortical visual

2018 Scientific reports

50. The Use of Physiological Signals in Brainstem/Midbrain fMRI Full Text available with Trip Pro

The Use of Physiological Signals in Brainstem/Midbrain fMRI Brainstem and midbrain nuclei are closely linked to cognitive performance and autonomic function. To advance the localization in this area, precise functional imaging is fundamental. In this study, we used a sophisticated fMRI technique as well as physiological recordings to investigate the involvement of brainstem/midbrain nuclei in cognitive control during a Stroop task. The temporal signal-to-noise ratio (tSNR) increased due (...) to physiological noise correction (PNC) especially in regions adjacent to arteries and cerebrospinal fluid. Within the brainstem/cerebellum template an average tSNR of 68 ± 16 was achieved after the simultaneous application of a high-resolution fMRI, specialized co-registration, and PNC. The analysis of PNC data revealed an activation of the substantia nigra in the Stroop interference contrast whereas no significant results were obtained in the midbrain or brainstem when analyzing uncorrected data

2018 Frontiers in neuroscience

51. mGluR1-Dependent Long Term Depression in Rodent Midbrain Dopamine Neurons Is Regulated by Neuregulin 1/ErbB Signaling Full Text available with Trip Pro

mGluR1-Dependent Long Term Depression in Rodent Midbrain Dopamine Neurons Is Regulated by Neuregulin 1/ErbB Signaling Increasing evidence demonstrates that the neurotrophic factor Neuregulin 1 (NRG1) and its receptors, ErbB tyrosine kinases, modulate midbrain dopamine (DA) transmission. We have previously reported that NRG1/ErbB signaling is essential for proper metabotropic glutamate receptors 1 (mGluR1) functioning in midbrain DA neurons, thus the functional interaction between ErbB receptors

2018 Frontiers in molecular neuroscience

52. HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons Full Text available with Trip Pro

HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons Environmental and genetic risk factors contribute to Parkinson's Disease (PD) pathogenesis and the associated midbrain dopamine (mDA) neuron loss. Here, we identify early PD pathogenic events by developing methodology that utilizes recent innovations in human pluripotent stem cells (hPSC) and chemical sensors of HSP90-incorporating chaperome networks. We show

2018 Nature communications

53. Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors Full Text available with Trip Pro

Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors Stressful life events are primary environmental factors that markedly contribute to depression by triggering brain cellular maladaptations. Dysregulation of ventral tegmental area (VTA) dopamine neurons has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, the relevant inputs that shape these dopamine signals

2018 Nature communications

55. Antero posterior elongation of midbrain in traumatic brain injury- significant sign yet a mistaken entity. (Abstract)

Antero posterior elongation of midbrain in traumatic brain injury- significant sign yet a mistaken entity. Antero posterior elongation of the midbrain is observed occasionally in severe traumatic brain injury and generally implies a bad outcome. The objective of the study was to document midbrain elongation and identify the implications of this finding.This prospective study included 100 patients with traumatic intracranial haematoma of more than 20 cc in volume. Key measurements were taken (...) in the midbrain and pontine regions and the status of perimesencephalic basal cisterns was noted. All the predictors were analyzed for the outcome.In twenty-nine patients the distorted midbrain appeared to be elongated in the antero posterior direction on visual inspection of CT head images. However, on statistical analysis, it was made out that there is no demonstrable anteroposterior lengthening of the midbrain. The factors influencing the appearance and outcome were discussed.Although not a true sign

2018 British Journal of Neurosurgery

56. Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis: A Randomized Clinical Trial. Full Text available with Trip Pro

Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis: A Randomized Clinical Trial. Cannabidiol (CBD) has antipsychotic effects in humans, but how these are mediated in the brain remains unclear.To investigate the neurocognitive mechanisms that underlie the therapeutic effects of CBD in psychosis.In this parallel-group, double-blind, placebo-controlled randomized clinical trial conducted at the South London and Maudsley NHS (...) ; IQR, -0.022 to 0.056; P < .001) and in the parahippocampal gyrus and midbrain during recall (placebo: median, 0.002; IQR, -0.016 to 0.010; control: median, 0.035; IQR, 0.015 to 0.039; P < .001). Within these 3 regions, activation in the CBD group was greater than in the placebo group but lower than in the control group (parahippocampal gyrus/midbrain: CBD: median, -0.013; IQR, -0.027 to 0.002; placebo: median, -0.007; IQR, -0.019 to 0.008; control: median, 0.034; IQR, 0.005 to 0.059); the level

2018 JAMA psychiatry (Chicago, Ill.) Controlled trial quality: predicted high

57. Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling. Full Text available with Trip Pro

Ventral midbrain astrocytes display unique physiological features and sensitivity to dopamine D2 receptor signaling. Astrocytes are ubiquitous CNS cells that support tissue homeostasis through ion buffering, neurotransmitter recycling, and regulation of CNS vasculature. Yet, despite the essential functional roles they fill, very little is known about the physiology of astrocytes in the ventral midbrain, a region that houses dopamine-releasing neurons and is critical for reward learning (...) and motivated behaviors. Here, using a combination of whole-transcriptome sequencing, histology, slice electrophysiology, and calcium imaging, we performed the first functional and molecular profiling of ventral midbrain astrocytes and observed numerous differences between these cells and their telencephalic counterparts, both in their gene expression profile and in their physiological properties. Ventral midbrain astrocytes have very low membrane resistance and inward-rectifying potassium channel-mediated

2018 Neuropsychopharmacology

58. Neuromelanin imaging and midbrain volumetry in progressive supranuclear palsy and Parkinson's disease. (Abstract)

Neuromelanin imaging and midbrain volumetry in progressive supranuclear palsy and Parkinson's disease. Background Nigral degeneration patterns differ between PSP and PD. However, the relationship between nigral degeneration and midbrain atrophy in PSP remains unclear. Objective We analyzed differences and relationships between nigral degeneration and midbrain atrophy in PSP and PD. Methods Neuromelanin-sensitive MRI and midbrain volumetry were performed in 11 PSP patients, 24 PD patients (...) , and 10 controls to measure the neuromelanin-sensitive SNpc area and midbrain volume. Results The neuromelanin-sensitive SNpc area and midbrain volume were significantly smaller in PSP patients compared with PD patients and controls. Motor deficits were inversely correlated with neuromelanin-sensitive SNpc area in PD, but not PSP patients. There was no significant correlation between neuromelanin-sensitive SNpc area and midbrain volume in either disease group. Midbrain volumetry discriminated PSP from

2018 Movement Disorders

59. Analysis of neurotrophic and antioxidant factors related to midbrain dopamine neuronal loss and brain inflammation in the cerebrospinal fluid of the elderly. (Abstract)

Analysis of neurotrophic and antioxidant factors related to midbrain dopamine neuronal loss and brain inflammation in the cerebrospinal fluid of the elderly. Midbrain dopamine neuronal loss and neuroinflammation are two phenomena that are associated with brain senescence. Neurotrophic factor changes and oxidative stress could subserve these phenomena. Aging-related brain changes can be well monitored through the cerebrospinal fluid (CSF). The objective was to analyze neurotrophic and oxidative (...) parameters that could be related to midbrain dopamine neuronal loss or brain inflammation in the CSF of elderly subjects: 1) levels of the dopaminotrophic factors BDNF, GDNF, persephin, and neurturin, 2) levels of the proinflammatory factors TGFβ1 and TGFβ2; 3) activity of main antioxidant enzymes (catalases, glutathione-peroxidase, glutathione-reductase, glutathione-S-transferases, peroxirredoxins, and superoxide-dismutases), 4) ferritin content, antioxidant protein which reduces reactive free iron

2018 Experimental Gerontology

60. Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator. Full Text available with Trip Pro

Increased spontaneous firing rates in auditory midbrain following noise exposure are specifically abolished by a Kv3 channel modulator. Noise exposure has been shown to produce long-lasting increases in spontaneous activity in central auditory structures in animal models, and similar pathologies are thought to contribute to clinical phenomena such as hyperacusis or tinnitus in humans. Here we demonstrate that multi-unit spontaneous neuronal activity in the inferior colliculus (IC) of mice (...) . Administration of the compound produced some reduction in the magnitude of evoked responses to a broadband noise, but unlike effects on spontaneous rates, these effects on evoked responses were not specific to recording sites with frequency tuning within the noise exposure band. Thus, the results suggest that modulators of Kv3 channels can selectively counteract increases in spontaneous activity in the auditory midbrain associated with noise exposure.Copyright © 2018 Elsevier B.V. All rights reserved.

2018 Hearing Research

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