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Midbrain

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21. Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons (Full text)

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 PubMed

22. 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)

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 PubMed

23. miR-182-5p and miR-183-5p Act as GDNF Mimics in Dopaminergic Midbrain Neurons (Full text)

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 PubMed

24. Author Correction: Midbrain circuit regulation of individual alcohol drinking behaviors in mice (Full text)

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 PubMed

25. Optogenetic auditory fMRI reveals the effects of visual cortical inputs on auditory midbrain response (Full text)

Optogenetic auditory fMRI reveals the effects of visual cortical inputs on auditory midbrain response Sensory cortices contain extensive descending (corticofugal) pathways, yet their impact on brainstem processing - particularly across sensory systems - remains poorly understood. In the auditory system, the inferior colliculus (IC) in the midbrain receives cross-modal inputs from the visual cortex (VC). However, the influences from VC on auditory midbrain processing are unclear. To investigate (...) sound processing in the auditory midbrain. Such combined optogenetic and auditory fMRI approach can shed light on the large-scale modulatory effects of corticofugal pathways and guide detailed electrophysiological studies in the future.

2018 Scientific reports PubMed

26. Phasic Stimulation of Midbrain Dopamine Neuron Activity Reduces Salt Consumption (Full text)

Phasic Stimulation of Midbrain Dopamine Neuron Activity Reduces Salt Consumption Salt intake is an essential dietary requirement, but excessive consumption is implicated in hypertension and associated conditions. Little is known about the neural circuit mechanisms that control motivation to consume salt, although the midbrain dopamine system, which plays a key role in other reward-related behaviors, has been implicated. We, therefore, examined the effects on salt consumption of either

2018 eNeuro PubMed

27. Circadian and Homeostatic Modulation of Multi-Unit Activity in Midbrain Dopaminergic Structures (Full text)

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

2018 Scientific reports PubMed

28. Zinc and linoleic acid pre-treatment attenuates biochemical and histological changes in the midbrain of rats with rotenone-induced Parkinsonism (Full text)

Zinc and linoleic acid pre-treatment attenuates biochemical and histological changes in the midbrain of rats with rotenone-induced Parkinsonism Studies have suggested the supplementation of Zinc and Linoleic acid in the management of neurodegenerative disorders but none has investigated the combined effects. Little is known about the neuroprotective effects of either Zinc or Linoleic acid or their combination against development of Parkinsonism. This study was designed to investigate (...) of both, 2 weeks prior to rotenone injection. Groups II and VI served as negative (rotenone group) and positive (Levodopa groups) controls respectively. Oxidative stress levels were assessed by estimating Lipid peroxidation (MDA), total antioxidant capacity, Superoxide dismutase, reduced Glutathione (GSH), glutathione peroxidase and catalase in the midbrain. Histological examination was done to assess structural changes in the midbrain.There was a significant prevention in lipid peroxidation

2018 BMC neuroscience PubMed

29. Sequential Role of SOXB2 Factors in GABAergic Neuron Specification of the Dorsal Midbrain (Full text)

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

2018 Frontiers in molecular neuroscience PubMed

30. A Zeb2-miR-200c loop controls midbrain dopaminergic neuron neurogenesis and migration (Full text)

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 PubMed

31. TLR9 activation via microglial glucocorticoid receptors contributes to degeneration of midbrain dopamine neurons (Full text)

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 PubMed

32. Parrots have evolved a primate-like telencephalic-midbrain-cerebellar circuit (Full text)

Parrots have evolved a primate-like telencephalic-midbrain-cerebellar circuit It is widely accepted that parrots show remarkable cognitive abilities. In mammals, the evolution of complex cognitive abilities is associated with increases in the size of the telencephalon and cerebellum as well as the pontine nuclei, which connect these two regions. Parrots have relatively large telencephalons that rival those of primates, but whether there are also evolutionary changes in their telencephalon

2018 Scientific reports PubMed

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

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

2018 Neural plasticity PubMed

34. Response dynamics of midbrain dopamine neurons and serotonin neurons to heroin, nicotine, cocaine, and MDMA (Full text)

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 PubMed

36. Bilateral Vertical Gaze Palsy after Cerebral Digital Subtraction Angiography Due to Unilateral Midbrain Infarction (Full text)

Bilateral Vertical Gaze Palsy after Cerebral Digital Subtraction Angiography Due to Unilateral Midbrain Infarction 29560622 2018 08 10 2018 11 14 2092-9382 32 2 2018 04 Korean journal of ophthalmology : KJO Korean J Ophthalmol Bilateral Vertical Gaze Palsy after Cerebral Digital Subtraction Angiography Due to Unilateral Midbrain Infarction. 154-156 10.3341/kjo.2017.0065 Kim Jong Hoon JH Department of Neurosurgery, Yeungnam University College of Medicine, Daegu, Korea. Kim Won Jae WJ Department

2018 Korean journal of ophthalmology : KJO PubMed

37. Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice (Full text)

Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice Animals respond to environmental threats, e.g. looming visual stimuli, with innate defensive behaviors such as escape and freezing. The key neural circuits that participate in the generation of such dimorphic defensive behaviors remain unclear. Here we show that the dimorphic behavioral patterns triggered by looming visual stimuli are mediated by parvalbumin-positive (PV+) projection neurons

2018 Nature communications PubMed

38. Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors (Full text)

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 PubMed

39. HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons (Full text)

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 PubMed

40. The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation (Full text)

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 PubMed

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