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61. 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

62. TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons Full Text available with Trip Pro

TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons Inflammation is a characteristic feature of Parkinson's disease (PD). We examined the role of TLR9 and its regulation by glucocorticoid receptors (GRs) in degeneration of substantia nigra dopamine neurons (DNs). TLR9 agonist, CpG-ODN, induced DN degeneration in mice lacking GR in microglia but not in controls. TLR9 deletion reduced DN loss in neurotoxin, 1-methyl-4-phenyl-1,2,3,6

2018 Nature communications

63. 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

64. 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

65. 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

66. 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

67. A rare case of Bruns syndrome with bilateral superior oblique palsy and dorsal midbrain syndrome. (Abstract)

A rare case of Bruns syndrome with bilateral superior oblique palsy and dorsal midbrain syndrome. We report a case of an 11-year-old boy referred for evaluation of esotropia associated with a 4-year history of intermittent headaches and vomiting triggered by sudden movements, such as sneezing and coughing. Magnetic resonance imaging (MRI) performed 3 years previously was reported to be normal. A thorough clinical examination revealed the clinical features of Dorsal midbrain syndrome with Bruns

2017 JAAPOS - Journal of the American Association for Pediatric Ophthalmology and Strabismus

68. Physiology of midbrain head movement neurons in cervical dystonia. Full Text available with Trip Pro

Physiology of midbrain head movement neurons in cervical dystonia. Early theories for cervical dystonia, as promoted by Hassler, emphasized the role of the midbrain interstitial nucleus of Cajal. Focus then shifted to the basal ganglia, and it was further supported with the success of deep brain stimulation. Contemporary theories suggested the role of the cerebellum, but even more recent hypotheses renewed interest in the midbrain. Although the pretectum was visited on several occasions, we (...) still do not know about the physiology of midbrain neurons in cervical dystonia.We analyzed the unique database of pretectal neurons collected in the 1970s and 1980s during historic stereotactic surgeries aimed to treat cervical dystonia. This database is valuable because such recordings could otherwise never be obtained from humans.We found the following 3 types of eye or neck movement sensitivity: eye-only neurons responded to pure vertical eye movements, neck-only neurons were sensitive to pure

2017 Movement Disorders

69. Severe Bilateral Kinetic Tremor Due to Unilateral Midbrain Lesions Full Text available with Trip Pro

Severe Bilateral Kinetic Tremor Due to Unilateral Midbrain Lesions The dentatothalamic tract connects the dentate nucleus of the cerebellum with the contralateral thalamus and plays a major role in the pathogenesis of tremor. Unilateral lesions of the dentatothalamic pathway may affect its ipsilateral predecussational or its contralateral postdecussational course, which results either in ipsilateral or in contralateral tremor.Here, we present two patients with a unilateral midbrain lesion

2017 Tremor and Other Hyperkinetic Movements

70. Holmes Tremor Secondary to a Stabbing Lesion in the Midbrain Full Text available with Trip Pro

Holmes Tremor Secondary to a Stabbing Lesion in the Midbrain The development of Holmes tremor (HT) after a direct lesion of the midbrain has rarely been reported in the literature, although several etiologies have been linked with HT, such as stroke, brainstem tumors, multiple sclerosis, head trauma, or infections.A 31-year-old male, having been stabbed in the right eye, presented with a rest and action tremor in the left upper limb associated with left hemiparesis with corresponding post

2017 Tremor and Other Hyperkinetic Movements

71. TNF superfamily member APRIL enhances midbrain dopaminergic axon growth and contributes to the nigrostriatal projection in vivo Full Text available with Trip Pro

TNF superfamily member APRIL enhances midbrain dopaminergic axon growth and contributes to the nigrostriatal projection in vivo We have studied the role of the tumor necrosis factor superfamily member APRIL in the development of embryonic mouse midbrain dopaminergic neurons in vitro and in vivo. In culture, soluble APRIL enhanced axon growth during a window of development between E12 and E14 when nigrostriatal axons are growing to their targets in the striatum in vivo. April transcripts were (...) detected in both the striatum and midbrain during this period and at later stages. The axon growth-enhancing effect of APRIL was similar to that of glial cell-derived neurotrophic factor (GDNF), but in contrast to GDNF, APRIL did not promote the survival of midbrain dopaminergic neurons. The effect of APRIL on axon growth was prevented by function-blocking antibodies to one of its receptors, BCMA (TNFRSF13A), but not by function-blocking antibodies to the other APRIL receptor, TACI (TNFRSF13B

2017 Experimental neurology

72. Midbrain circuit regulation of individual alcohol drinking behaviors in mice Full Text available with Trip Pro

Midbrain circuit regulation of individual alcohol drinking behaviors in mice Alcohol-use disorder (AUD) is the most prevalent substance-use disorder worldwide. There is substantial individual variability in alcohol drinking behaviors in the population, the neural circuit mechanisms of which remain elusive. Utilizing in vivo electrophysiological techniques, we find that low alcohol drinking (LAD) mice have dramatically higher ventral tegmental area (VTA) dopamine neuron firing and burst activity

2017 Nature communications

73. Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage Full Text available with Trip Pro

Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage Higher stages of central auditory processing compensate for a loss of cochlear nerve synapses by increasing the gain on remaining afferent inputs, thereby restoring firing rate codes for rudimentary sound features. The benefits of this compensatory plasticity are limited, as the recovery of precise temporal coding is comparatively modest. We reasoned that persistent

2017 Scientific reports

74. Diversity of bilateral synaptic assemblies for binaural computation in midbrain single neurons. (Abstract)

Diversity of bilateral synaptic assemblies for binaural computation in midbrain single neurons. Binaural hearing confers many beneficial functions but our understanding of its underlying neural substrates is limited. This study examines the bilateral synaptic assemblies and binaural computation (or integration) in the central nucleus of the inferior colliculus (ICc) of the auditory midbrain, a key convergent center. Using in-vivo whole-cell patch-clamp, the excitatory and inhibitory

2017 Hearing Research

75. Impact of Roux-en-Y gastric bypass surgery on appetite, alcohol intake behaviors, and midbrain ghrelin signaling in the rat. Full Text available with Trip Pro

Impact of Roux-en-Y gastric bypass surgery on appetite, alcohol intake behaviors, and midbrain ghrelin signaling in the rat. Roux-en-Y gastric bypass (RYGB) surgery reduces appetite and stimulates new onset alcohol misuse; however, the genesis of these behavioral changes is unclear. This study is hypothesized that new onset alcohol intake is a behavioral adaptation that occurs secondary to reduced appetite and correlates with altered central ghrelin signaling.Hedonic high-fat diet (HFD) intake

2017 Obesity

76. Increasing GABA reverses age-related alterations in excitatory receptive fields and intensity coding of auditory midbrain neurons in aged mice. Full Text available with Trip Pro

Increasing GABA reverses age-related alterations in excitatory receptive fields and intensity coding of auditory midbrain neurons in aged mice. A key feature of age-related hearing loss is a reduction in the expression of inhibitory neurotransmitters in the central auditory system. This loss is partially responsible for changes in central auditory processing, as inhibitory receptive fields play a critical role in shaping neural responses to sound stimuli. Vigabatrin (VGB), an antiepileptic

2017 Neurobiology of Aging

77. The Effects of Age, from Young to Middle Adulthood, and Gender on Resting State Functional Connectivity of the Dopaminergic Midbrain Full Text available with Trip Pro

The Effects of Age, from Young to Middle Adulthood, and Gender on Resting State Functional Connectivity of the Dopaminergic Midbrain Dysfunction of the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is implicated in psychiatric disorders including attention-deficit/ hyperactivity disorder (ADHD), addiction, schizophrenia and movement disorders such as Parkinson's disease (PD). Although the prevalence of these disorders varies by age and sex, the underlying

2017 Frontiers in human neuroscience

78. Effects of diet and insulin on dopamine transporter activity and expression in rat caudate-putamen, nucleus accumbens, and midbrain Full Text available with Trip Pro

Effects of diet and insulin on dopamine transporter activity and expression in rat caudate-putamen, nucleus accumbens, and midbrain Food restriction (FR) and obesogenic (OB) diets are known to alter brain dopamine transmission and exert opposite modulatory effects on behavioral responsiveness to psychostimulant drugs of abuse. Mechanisms underlying these diet effects are not fully understood. In this study, we examined diet effects on expression and function of the dopamine transporter (DAT (...) ) in caudate-putamen (CPu), nucleus accumbens (NAc), and midbrain regions. Dopamine (DA) uptake by CPu, NAc or midbrain synapto(neuro)somes was measured in vitro with rotating disk electrode voltammetry or with [3 H]DA uptake and was found to correlate with DAT surface expression, assessed by maximal [3 H](-)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane binding and surface biotinylation assays. FR and OB diets were both found to decrease DAT activity in CPu with a corresponding decrease in surface

2017 Journal of neurochemistry

79. Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum Full Text available with Trip Pro

Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar (...) prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling

2017 The Journal of Neuroscience Controlled trial quality: uncertain

80. Reliable Identification of Living Dopaminergic Neurons in Midbrain Cultures Using RNA Sequencing and TH-promoter-driven eGFP Expression Full Text available with Trip Pro

Reliable Identification of Living Dopaminergic Neurons in Midbrain Cultures Using RNA Sequencing and TH-promoter-driven eGFP Expression In Parkinson's Disease (PD) there is widespread neuronal loss throughout the brain with pronounced degeneration of dopaminergic neurons in the SNc, leading to bradykinesia, rigidity, and tremor. The identification of living dopaminergic neurons in primary Ventral Mesencephalic (VM) cultures using a fluorescent marker provides an alternative way to study (...) RNA-Seq libraries1,2,3,4,5. After passing a quality-control check, single-cell libraries are sequenced and subsequent analysis is carried out to measure gene expression. We report transcriptome results for individual dopaminergic and GABAergic neurons isolated from midbrain cultures. We report that 100% of the live TH-eGFP cells that were harvested and sequenced were dopaminergic neurons. These techniques will have widespread applications in neuroscience and molecular biology.

2017 Journal of visualized experiments : JoVE

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