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Midbrain

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41. 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

42. 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

43. 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

44. 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

45. Impaired reward prediction error encoding and striatal-midbrain connectivity in depression. Full Text available with Trip Pro

Impaired reward prediction error encoding and striatal-midbrain connectivity in depression. Anhedonia (hyposensitivity to rewards) and negative bias (hypersensitivity to punishments) are core features of major depressive disorder (MDD), which could stem from abnormal reinforcement learning. Emerging evidence highlights blunted reward learning and reward prediction error (RPE) signaling in the striatum in MDD, although inconsistencies exist. Preclinical studies have clarified that ventral

2018 Neuropsychopharmacology

46. 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

47. An Anatomic Characterization of the Midbrain Near Response Neurons in the Macaque Monkey. Full Text available with Trip Pro

An Anatomic Characterization of the Midbrain Near Response Neurons in the Macaque Monkey. These experiments were designed to reveal the location of the premotor neurons that have previously been designated physiologically as the midbrain near response cells controlling vergence, lens accommodation, and pupillary constriction in response to target distance.To identify this population, the fixed N2c strain of rabies virus was injected into the ciliary body of seven Macaca fascicularis monkeys (...) cells making up a continuous column within the Edinger-Westphal nucleus. A population of premotor cells that likely represents the midbrain near response cells is located in the supraoculomotor area. These cells are bilaterally distributed relative to the eye they control, and are most numerous caudally.

2018 Investigative Ophthalmology & Visual Science

48. Survival of midbrain dopamine neurons depends on the Bcl2 factor Mcl1 Full Text available with Trip Pro

Survival of midbrain dopamine neurons depends on the Bcl2 factor Mcl1 Mitochondria-dependent apoptosis plays an important role in the embryonic development of the midbrain dopaminergic system as well as in Parkinson's disease. Central to mitochondria-dependent apoptosis is the Bcl2 family of apoptosis-regulating proteins. However, it was unclear which Bcl2 proteins are important for the survival of dopaminergic neurons. Here, we identify Mcl1 as a critical Bcl2 pro-survival factor in midbrain (...) , activation of cleaved caspase-3 and finally cell death. The dependence of mouse dopaminergic midbrain neurons on Mcl1 was confirmed using ex vivo slice cultures from Pitx3GFP/+ and wildtype mice. In mouse dopaminergic midbrain neurons positive for the midbrain dopaminergic marker Pitx3, or tyrosine hydroxylase, UMI-77 treatment caused a dramatic increase in cleaved caspase 3, indicating that Mcl1 activity is required for basal neuronal survival. Overall, our results suggest that Mcl1 is of critical

2018 Cell Death Discovery

49. Neurophilic Descending Migration of Dorsal Midbrain Neurons Into the Hindbrain Full Text available with Trip Pro

Neurophilic Descending Migration of Dorsal Midbrain Neurons Into the Hindbrain Stereotypic cell migrations in the developing brain are fundamental for the proper patterning of brain regions and formation of neural networks. In this work, we uncovered in the developing rat, a population of neurons expressing tyrosine hydroxylase (TH) that migrates posteriorly from the alar plate of the midbrain, in neurophilic interaction with axons of the mesencephalic nucleus of the trigeminal nerve (...) . A fraction of this population was also shown to traverse the mid-hindbrain boundary, reaching the vicinity of the locus coeruleus (LC) in rhombomere 1 (r1). This migratory population, however, does not have a noradrenergic (NA) phenotype and, in keeping with its midbrain origin, expresses Otx2 which is down regulated upon migration into the hindbrain. The interaction with the trigeminal mesencephalic axons is necessary for the arrangement and distribution of migratory cells as these aspects

2018 Frontiers in neuroanatomy

50. Midbrain circuits that set locomotor speed and gait selection Full Text available with Trip Pro

Midbrain circuits that set locomotor speed and gait selection Locomotion is a fundamental motor function common to the animal kingdom. It is implemented episodically and adapted to behavioural needs, including exploration, which requires slow locomotion, and escape behaviour, which necessitates faster speeds. The control of these functions originates in brainstem structures, although the neuronal substrate(s) that support them have not yet been elucidated. Here we show in mice that speed (...) and gait selection are controlled by glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). GlutNs in both of these regions contribute to the control of slower, alternating-gait locomotion, whereas only GlutNs in the CnF are able to elicit high-speed, synchronous-gait locomotion. Additionally, both the activation dynamics and the input and output connectivity matrices of GlutNs in the PPN and the CnF

2018 Nature

51. Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons Full Text available with Trip Pro

Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons Parkinson's disease is characterized by the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). DA neurons in the ventral tegmental area are more resistant to this degeneration than those in the SNc, though the mechanisms for selective resistance or vulnerability remain poorly understood. A key to elucidating these processes may lie within the subset of DA neurons that corelease glutamate and express

2018 The Journal of clinical investigation

52. miR-182-5p and miR-183-5p Act as GDNF Mimics in Dopaminergic Midbrain Neurons Full Text available with Trip Pro

miR-182-5p and miR-183-5p Act as GDNF Mimics in Dopaminergic Midbrain Neurons Parkinson's disease (PD) is the second-most-frequent neurodegenerative disorder worldwide. One major hallmark of PD is the degeneration of dopaminergic (DA) neurons in the substantia nigra. Glial cell line-derived neurotrophic factor (GDNF) potently increases DA neuron survival in models of PD; however, the underlying mechanisms are incompletely understood. MicroRNAs (miRNAs) are small, non-coding RNAs (...) that are important for post-transcriptional regulation of gene expression. Using small RNA sequencing, we show that GDNF specifically increases the expression of miR-182-5p and miR-183-5p in primary midbrain neurons (PMNs). Transfection of synthetic miR-182-5p and miR-183-5p mimics leads to increased neurite outgrowth and mediates neuroprotection of DA neurons in vitro and in vivo, mimicking GDNF effects. This is accompanied by decreased expression of FOXO3 and FOXO1 transcription factors and increased PI3K-Akt

2018 Molecular therapy. Nucleic acids

53. Author Correction: Midbrain circuit regulation of individual alcohol drinking behaviors in mice Full Text available with Trip Pro

Author Correction: Midbrain circuit regulation of individual alcohol drinking behaviors in mice The original version of this Article contained an error in the spelling of the author Scott Edwards, which was incorrectly given as Scott Edward. This has now been corrected in both the PDF and HTML versions of the Article.

2018 Nature communications

54. Development of the Mechanisms Governing Midbrain Multisensory Integration Full Text available with Trip Pro

Development of the Mechanisms Governing Midbrain Multisensory Integration The ability to integrate information across multiple senses enhances the brain's ability to detect, localize, and identify external events. This process has been well documented in single neurons in the superior colliculus (SC), which synthesize concordant combinations of visual, auditory, and/or somatosensory signals to enhance the vigor of their responses. This increases the physiological salience of crossmodal events (...) with crossmodal cues is acquired. Recent empirical findings suggest that the mechanisms supporting this development must be more complex than previously believed. The present work integrates these data with what is already known about the underlying circuit in the midbrain to create and test a mechanistic model of multisensory development. This model represents a novel and comprehensive framework that explains how midbrain circuits acquire multisensory experience and reveals how disruptions in this neurotypic

2018 The Journal of Neuroscience

55. The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model Full Text available with Trip Pro

The effect of exercise frequency on neuropathic pain and pain-related cellular reactions in the spinal cord and midbrain in a rat sciatic nerve injury model Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular (...) and astrocytes), expression of brain-derived neurotrophic factor (BDNF) and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone) were administered using intraperitoneal injection.The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic

2018 Journal of pain research

56. Why acute unilateral vestibular midbrain lesions rarely manifest with rotational vertigo: a clinical and modelling approach to head direction cell function Full Text available with Trip Pro

Why acute unilateral vestibular midbrain lesions rarely manifest with rotational vertigo: a clinical and modelling approach to head direction cell function A retrospective clinical study focused on the frequency of rotational vertigo in 63 patients with acute unilateral midbrain strokes involving the vestibular and ocular motor systems. In contrast to unilateral pontomedullary brainstem lesions, rotational vertigo in midbrain lesions occurred with a low frequency (14%) and transient (< 1 day (...) ) course. Swaying vertigo or unspecific dizziness (22%) and postural imbalance (31%) were more frequent. Midbrain strokes with transient rotational vertigo manifested with lesions chiefly in the caudal midbrain tegmentum, while manifestations with swaying, unspecific, or no vertigo chiefly occurred in rostral mesencephalic or meso-diencephalic lesions. We hypothesize that these different manifestations can be explained by the distribution of two separate cell systems based on semicircular canal

2018 Journal of neurology

57. Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA Full Text available with Trip Pro

Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA Heroin, nicotine, cocaine, and MDMA are abused by billions of people. They are believed to target midbrain dopamine neurons and/or serotonin neurons, but their effects on the dynamic neuronal activity remain unclear in behaving states. By combining cell-type-specific fiber photometry of Ca2+ signals and intravenous drug infusion, here we show that these four drugs of abuse profoundly (...) modulate the activity of mouse midbrain dopamine neurons and serotonin neurons with distinct potency and kinetics. Heroin strongly activates dopamine neurons, and only excites serotonin neurons at higher doses. Nicotine activates dopamine neurons in merely a few seconds, but produces minimal effects on serotonin neurons. Cocaine and MDMA cause long-lasting suppression of both dopamine neurons and serotonin neurons, although MDMA inhibits serotonin neurons more profoundly. Moreover, these inhibitory

2018 Cell Discovery

59. A Zeb2-miR-200c loop controls midbrain dopaminergic neuron neurogenesis and migration Full Text available with Trip Pro

A Zeb2-miR-200c loop controls midbrain dopaminergic neuron neurogenesis and migration Zeb2 is a homeodomain transcription factor that plays pleiotropic functions during embryogenesis, but its role for midbrain dopaminergic (mDA) neuron development is unknown. Here we report that Zeb2 is highly expressed in progenitor cells in the ventricular zone of the midbrain floor plate and downregulated in postmitotic neuroblasts. Functional experiments show that Zeb2 expression in the embryonic ventral (...) midbrain is dynamically regulated by a negative feedback loop that involves miR-200c. We also find that Zeb2 overexpression reduces the levels of CXCR4, NR4A2, and PITX3 in the developing ventral midbrain in vivo, resulting in migration and mDA differentiation defects. This phenotype was recapitulated by miR-200c knockdown, suggesting that the Zeb2-miR-200c loop prevents the premature differentiation of mDA progenitors into postmitotic cells and their migration. Together, our study establishes Zeb2

2018 Communications Biology

60. BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In Vivo and in Human Induced Pluripotent and Neural Stem Cells Full Text available with Trip Pro

BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In Vivo and in Human Induced Pluripotent and Neural Stem Cells The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, which are currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell (...) signaling as a novel essential pathway regulating the development of mammalian midbrain dopaminergic (mDA) neurons in vivo and provide insights into the molecular mechanisms of this process. BMP5/7 regulate MSX1/2 (msh homeobox 1/2) and SHH (sonic hedgehog) expression to direct mDA neurogenesis. Moreover, the BMP signaling component SMAD1 controls the differentiation of mDA progenitors, particularly to substantia nigra neurons, by directing their cell cycle exit. Importantly, BMP5/7 increase robustly

2018 The Journal of Neuroscience

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