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Midbrain

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1. Speech-in-noise representation in the aging midbrain and cortex: Effects of hearing loss. (PubMed)

Speech-in-noise representation in the aging midbrain and cortex: Effects of hearing loss. Age-related deficits in speech-in-noise understanding pose a significant problem for older adults. Despite the vast number of studies conducted to investigate the neural mechanisms responsible for these communication difficulties, the role of central auditory deficits, beyond peripheral hearing loss, remains unclear. The current study builds upon our previous work that investigated the effect of aging (...) on normal-hearing individuals and aims to estimate the effect of peripheral hearing loss on the representation of speech in noise in two critical regions of the aging auditory pathway: the midbrain and cortex. Data from 14 hearing-impaired older adults were added to a previously published dataset of 17 normal-hearing younger adults and 15 normal-hearing older adults. The midbrain response, measured by the frequency-following response (FFR), and the cortical response, measured

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2019 PLoS ONE

2. Vertical diplopia and oscillopsia due to midbrain keyhole aqueduct syndrome associated with severe cough (PubMed)

Vertical diplopia and oscillopsia due to midbrain keyhole aqueduct syndrome associated with severe cough Midline structural defects in the neural axis can give rise to neuro-ophthalmic symptoms. We report a rare case of keyhole aqueduct syndrome presenting after two years of severe cough due to gastroesophageal reflux disease.A 58-year-old woman with a 2-year history of daily, severe cough presented to the neuro-ophthalmology clinic with progressive diplopia and oscillopsia. Examination (...) in the ventral midbrain communicating with the cerebral aqueduct, consistent with keyhole aqueduct syndrome. Her nystagmus and diplopia improved with oral acetazolamide treatment, at high doses of 2500-3000 mg per day.We report the first case of midbrain keyhole aqueduct syndrome with ocular motor and other neuro-ophthalmic manifestations associated with severe cough. Although her cough was effectively treated and intracranial pressure measurement was normal, her ophthalmic symptoms continued to progress

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2018 American journal of ophthalmology case reports

3. Isolated Spontaneous Midbrain Hemorrhage in a 14-Year-Old Boy (PubMed)

Isolated Spontaneous Midbrain Hemorrhage in a 14-Year-Old Boy Isolated spontaneous midbrain hemorrhages are rare because they are usually secondary to hemorrhages from inferior structures such as the pons and cerebellum, or superior structures such as the thalamus and putamen. While the etiologies are largely unidentified, the most common ones are vascular malformations and bleeding diathesis with hypertension being relatively uncommon. We report midbrain hemorrhage in a 14-year-old boy (...) with a long-standing history of frequent migraine headaches and attention deficit/hyperactivity disorder (ADHD). Neurologic examinations, noncontrast computed tomography (CT) scans, and magnetic resonance imaging (MRI) suggested that the lesion likely affected the dorsal part of the midbrain. The neurologic symptoms improved following endoscopic third ventriculostomy (ETV) with the placement of external ventricular drains (EVDs). In this report, anatomical correlations to the case are discussed

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2017 Journal of neurological surgery reports

4. Cerebellar, limbic, and midbrain volume alterations in sudden unexpected death in epilepsy. (PubMed)

Cerebellar, limbic, and midbrain volume alterations in sudden unexpected death in epilepsy. The processes underlying sudden unexpected death in epilepsy (SUDEP) remain elusive, but centrally mediated cardiovascular or respiratory collapse is suspected. Volume changes in brain areas mediating recovery from extreme cardiorespiratory challenges may indicate failure mechanisms and allow prospective identification of SUDEP risk.We retrospectively imaged SUDEP cases (n = 25), patients comparable (...) with parahippocampal volume. Volumes of the bilateral anterior insula and midbrain in SUDEP cases were larger the closer to SUDEP from magnetic resonance imaging.SUDEP victims show significant tissue loss in areas essential for cardiorespiratory recovery and enhanced volumes in areas that trigger hypotension or impede respiratory patterning. Those changes may shed light on SUDEP pathogenesis and prospectively detect patterns identifying those at risk.© 2019 The Authors. Epilepsia published by Wiley Periodicals

2019 Epilepsia

5. Binaural unmasking of the accuracy of envelope-signal representation in rat auditory cortex but not auditory midbrain. (PubMed)

Binaural unmasking of the accuracy of envelope-signal representation in rat auditory cortex but not auditory midbrain. Accurate neural representations of acoustic signals under noisy conditions are critical for animals' survival. Detecting signal against background noise can be improved by binaural hearing particularly when an interaural-time-difference (ITD) disparity is introduced between the signal and the noise, a phenomenon known as binaural unmasking. Previous studies have mainly focused

2019 Hearing Research

6. Modulation of midbrain neurocircuitry by intranasal insulin. (PubMed)

Modulation of midbrain neurocircuitry by intranasal insulin. Insulin modulates dopamine neuron activity in midbrain and affects processes underlying food intake behaviour, including impulsivity and reward processing. Here, we used intranasal administration and task-free functional MRI in humans to assess time- and dose-dependent effects of insulin on functional connectivity of the dopaminergic midbrain - and how these effects varied depending on systemic insulin sensitivity as measured by HOMA (...) -IR. Specifically, we used a repeated-measures design with factors dose (placebo, 40 IU, 100 IU, 160 IU), time (7 time points during a 90 min post-intervention interval), and group (low vs. high HOMA-IR). A factorial analysis identified a three-way interaction (with whole-brain significance) with regard to functional connectivity between midbrain and the ventromedial prefrontal cortex. This interaction demonstrates that systemic insulin sensitivity modulates the temporal course and dose-dependent

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2019 NeuroImage Controlled trial quality: uncertain

7. Neurophilic Descending Migration of Dorsal Midbrain Neurons Into the Hindbrain (PubMed)

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

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2018 Frontiers in neuroanatomy

8. Survival of midbrain dopamine neurons depends on the Bcl2 factor Mcl1 (PubMed)

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

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2018 Cell Death Discovery

9. Bilateral medial rectus palsy due to midbrain infarction following concussion head injury (PubMed)

Bilateral medial rectus palsy due to midbrain infarction following concussion head injury Here, we report a rare case of bilateral medial rectus palsy following closed head injury. An adult male had an accidental fall which rendered him unconscious. This was followed by diplopia and restricted ocular motility. He received supportive medical therapy. He was examined for systemic medical and ophthalmic findings. Routine laboratory tests and imaging techniques were employed as per the symptoms (...) . Diffusion-weighted imaging on magnetic resonance imaging proved it to be a rare presentation of small bilateral midbrain infarct. He recovered fully after 8 months.

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2018 Indian journal of ophthalmology

10. Changes to Neural Activation Patterns (c-fos Labeling) in Chinchilla Auditory Midbrain following Neonatal Exposure to an Enhanced Sound Environment (PubMed)

Changes to Neural Activation Patterns (c-fos Labeling) in Chinchilla Auditory Midbrain following Neonatal Exposure to an Enhanced Sound Environment Sensory brain regions show neuroplastic changes following deficits or experimental augmentation of peripheral input during a neonatal period. We have previously shown reorganization of cortical tonotopic maps after neonatal cochlear lesions or exposure to an enhanced acoustic environment. Such experiments probe the cortex and show reorganization (...) , but it is unclear if such changes are intrinsically cortical or reflect projections from modified subcortical regions. Here, we ask whether an enhanced neonatal acoustic environment can induce midbrain (inferior colliculus (IC)) changes. Neonatal chinchillas were chronically exposed to a 70 dB SPL narrowband (2 ± 0.25 kHz) sound stimulus for 4 weeks. In line with previous studies, we hypothesized that such exposure would induce widening of the 2 kHz tonotopic map region in IC. To probe c-fos expression in IC

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2018 Neural plasticity

11. Midbrain circuits that set locomotor speed and gait selection (PubMed)

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

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2018 Nature

12. The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation (PubMed)

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

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2018 Stem cell reports

13. Sequential Role of SOXB2 Factors in GABAergic Neuron Specification of the Dorsal Midbrain (PubMed)

Sequential Role of SOXB2 Factors in GABAergic Neuron Specification of the Dorsal Midbrain Studies proposed a model for embryonic neurogenesis where the expression levels of the SOXB2 and SOXB1 factors regulate the differentiation status of the neural stem cells. However, the precise role of the SOXB2 genes remains controversial. Therefore, this study aims to investigate the effects of individual deletions of the SOX21 and SOX14 genes during the development of the dorsal midbrain. We show (...) that SOX21 and SOX14 function distinctly during the commitment of the GABAergic lineage. More explicitly, deletion of SOX21 reduced the expression of the GABAergic precursor marker GATA3 and BHLHB5 while the expression of GAD6, which marks GABAergic terminal differentiation, was not affected. In contrast deletion of SOX14 alone was sufficient to inhibit terminal differentiation of the dorsal midbrain GABAergic neurons. Furthermore, we demonstrate through gain-of-function experiments, that despite

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2018 Frontiers in molecular neuroscience

14. Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons (PubMed)

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

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2018 The Journal of clinical investigation

15. Correction: Altered activation and connectivity in a hippocampal–basal ganglia–midbrain circuit during salience processing in subjects at ultra high risk for psychosis (PubMed)

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.

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2018 Translational psychiatry

16. Neurotransmitter identity and electrophysiological phenotype are genetically coupled in midbrain dopaminergic neurons (PubMed)

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

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2018 Scientific reports

17. Activation of the P2X7 receptor in midbrain periaqueductal gray participates in the analgesic effect of tramadol in bone cancer pain rats (PubMed)

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

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2018 Molecular pain

18. Transcriptomic analysis of left-right differences in human embryonic forebrain and midbrain (PubMed)

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.

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2018 Scientific data

19. Manipulating midbrain dopamine neurons and reward-related behaviors with light-controllable nicotinic acetylcholine receptors (PubMed)

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

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2018 eLife

20. Circadian and Homeostatic Modulation of Multi-Unit Activity in Midbrain Dopaminergic Structures (PubMed)

Circadian and Homeostatic Modulation of Multi-Unit Activity in Midbrain Dopaminergic Structures Although the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical neuronal activity in midbrain ventral-tegmental-area (...) and VTA. Six-hours of sleep deprivation induced a significant depression of neuronal activity in both areas. Surprisingly, these alterations lasted for up to 48 hours and persisted even after the normalization of cortical EEG waves. Our results show that sleep and sleep disturbances significantly affect neuronal activity in midbrain DA structures. We propose that these changes in neuronal activity underlie the well-known relationship between sleep alterations and several disorders involving

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2018 Scientific reports

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