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Midbrain

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161. Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons Full Text available with Trip Pro

Lmx1a and Lmx1b regulate mitochondrial functions and survival of adult midbrain dopaminergic neurons The LIM-homeodomain transcription factors Lmx1a and Lmx1b play critical roles during the development of midbrain dopaminergic progenitors, but their functions in the adult brain remain poorly understood. We show here that sustained expression of Lmx1a and Lmx1b is required for the survival of adult midbrain dopaminergic neurons. Strikingly, inactivation of Lmx1a and Lmx1b recreates cellular

2016 Proceedings of the National Academy of Sciences of the United States of America

162. Sharp temporal tuning in the bat auditory midbrain overcomes spectral-temporal trade-off imposed by cochlear mechanics Full Text available with Trip Pro

Sharp temporal tuning in the bat auditory midbrain overcomes spectral-temporal trade-off imposed by cochlear mechanics In the cochlea of the mustached bat, cochlear resonance produces extremely sharp frequency tuning to the dominant frequency of the echolocation calls, around 61 kHz. Such high frequency resolution in the cochlea is accomplished at the expense of losing temporal resolution because of cochlear ringing, an effect that is observable not only in the cochlea but also in the cochlear (...) nucleus. In the midbrain, the duration of sounds is thought to be analyzed by duration-tuned neurons, which are selective to both stimulus duration and frequency. We recorded from 57 DTNs in the auditory midbrain of the mustached bat to assess if a spectral-temporal trade-off is present. Such spectral-temporal trade-off is known to occur as sharp tuning in the frequency domain which results in poorer resolution in the time domain, and vice versa. We found that a specialized sub-population of midbrain

2016 Scientific reports

163. Protection of Primary Dopaminergic Midbrain Neurons by GPR139 Agonists Supports Different Mechanisms of MPP+ and Rotenone Toxicity Full Text available with Trip Pro

Protection of Primary Dopaminergic Midbrain Neurons by GPR139 Agonists Supports Different Mechanisms of MPP+ and Rotenone Toxicity The G-protein coupled receptor 139 (GPR139) is expressed specifically in the brain in areas of relevance for motor control. GPR139 function and signal transduction pathways are elusive, and results in the literature are even contradictory. Here, we examined the potential neuroprotective effect of GPR139 agonism in primary culture models of dopaminergic (DA) neuronal

2016 Frontiers in cellular neuroscience

164. Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells Full Text available with Trip Pro

Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells Understanding human embryonic ventral midbrain is of major interest for Parkinson's disease. However, the cell types, their gene expression dynamics, and their relationship to commonly used rodent models remain to be defined. We performed single-cell RNA sequencing to examine ventral midbrain development in human and mouse. We found 25 molecularly defined human cell types, including five subtypes of radial glia-like (...) , our study provides insight into the molecular programs controlling human midbrain development and provides a foundation for the development of cell replacement therapies.Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

2016 Cell

165. Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1 Full Text available with Trip Pro

Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1 Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (mDA) neurons for cell replacement therapy for Parkinson's disease (PD). However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. To eliminate these unwanted cells, cell sorting using antibodies for specific markers such as CORIN or ALCAM has been developed (...) , but neither marker is specific for ventral midbrain. Here we employ a double selection strategy for cells expressing both CORIN and LMX1A::GFP, and report a cell surface marker to enrich mDA progenitors, LRTM1. When transplanted into 6-OHDA-lesioned rats, human iPSC-derived LRTM1+ cells survive and differentiate into mDA neurons in vivo, resulting in a significant improvement in motor behaviour without tumour formation. In addition, there was marked survival of mDA neurons following transplantation

2016 Nature communications

166. Neuroprotective Effects of 7, 8-dihydroxyflavone on Midbrain Dopaminergic Neurons in MPP+-treated Monkeys Full Text available with Trip Pro

Neuroprotective Effects of 7, 8-dihydroxyflavone on Midbrain Dopaminergic Neurons in MPP+-treated Monkeys Parkinson's disease (PD) is one common neurodegenerative disease caused by a significant loss of midbrain dopaminergic neurons. Previous reports showed that 7, 8- dihydroxyflavone (7, 8-DHF) as a potent TrkB agonist can mimic BDNF and play neuroprotective roles for mouse dopaminergic neurons. Nonetheless, the safety and neuroprotective effects are unclear in monkey models of PD. Here, we (...) find that 7, 8-DHF could be absorbed and metabolized into 7-hydroxy-8-methoxyflavone through oral administration in monkeys. The half-life time of 7, 8-DHF in monkey plasma is about 4-8 hrs. Furthermore, these monkeys maintain health state throughout the course of seven-month treatments of 7, 8-DHF (30 mg/kg/day). Importantly, 7, 8-DHF treatments can prevent the progressive degeneration of midbrain dopaminergic neurons by attenuating neurotoxic effects of MPP+ and display strong neuroprotective

2016 Scientific reports

167. Efficiently Specified Ventral Midbrain Dopamine Neurons from Human Pluripotent Stem Cells Under Xeno‐Free Conditions Restore Motor Deficits in Parkinsonian Rodents Full Text available with Trip Pro

Efficiently Specified Ventral Midbrain Dopamine Neurons from Human Pluripotent Stem Cells Under Xeno‐Free Conditions Restore Motor Deficits in Parkinsonian Rodents Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)-derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson's disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior

2016 Stem cells translational medicine

168. Embryonic origin and lineage hierarchies of the neural progenitor subtypes building the zebrafish adult midbrain Full Text available with Trip Pro

Embryonic origin and lineage hierarchies of the neural progenitor subtypes building the zebrafish adult midbrain Neurogenesis in the post-embryonic vertebrate brain varies in extent and efficiency between species and brain territories. Distinct neurogenesis modes may account for this diversity, and several neural progenitor subtypes, radial glial cells (RG) and neuroepithelial progenitors (NE), have been identified in the adult zebrafish brain. The neurogenic sequences issued from (...) these progenitors, and their contribution to brain construction, remain incompletely understood. Here we use genetic tracing techniques based on conditional Cre recombination and Tet-On neuronal birthdating to unravel the neurogenic sequence operating from NE progenitors in the zebrafish post-embryonic optic tectum. We reveal that a subpopulation of her5-positive NE cells of the posterior midbrain layer stands at the top of a neurogenic hierarchy involving, in order, the amplification pool of the tectal

2016 Developmental biology

169. Pilocytic Midbrain Astrocytoma Presenting with Fresh Bleed after Twenty-one-years Survival Following First Surgery: A Unique Case of Longest Brainstem Glioma Survival Full Text available with Trip Pro

Pilocytic Midbrain Astrocytoma Presenting with Fresh Bleed after Twenty-one-years Survival Following First Surgery: A Unique Case of Longest Brainstem Glioma Survival Brainstem glioma usually carries a poor prognosis and prolonged survival is very infrequent. In a detailed Pubmed, Medline search for prolonged survival, authors could got a longest survival only up to seventeen years, reported by Umehara et al, who was subjected to gamma knife therapy and got symptomatic, MRI brain reveled large (...) tumor growth during pregnancy necessitating emergency surgery and histopathological diagnosis was pilocytic astrocytoma. Authors report an interesting case of midbrain glioma diagnosed 21 years back, who underwent gross resection in the year 1993, histopathology was pilocytic astrocytoma, WHO grade I, and received gamma knife surgery for residual subsequently and he presented with sudden onset left sided hemiplegia on the current admission. The cranial MRI imaging revealed an infarct involving right

2016 Journal of neurosciences in rural practice

170. Tongue somatosensory evoked potentials reflect midbrain involvement in patients with clinically isolated syndrome Full Text available with Trip Pro

Tongue somatosensory evoked potentials reflect midbrain involvement in patients with clinically isolated syndrome To test the hypothesis that tSSEP findings reflect clinical and MRI MS lesions, the aim of this study was to investigate tSSEP changes in patients with clinically isolated syndrome (CIS) in relation to clinical and brainstem MRI findings. The second aim was to investigate whether the interpretation of the tSSEP results in the form of the tSSEP score enables better evaluation (...) =prolonged latency, 3=absent response) and the two values were summed.There was no difference in the absolute values of the tSSEP variables regarding the presence of clinical symptoms. No association was found between tSSEP abnormalities and clinical symptoms (P=0.544). Brainstem lesions (midbrain and pons) were associated with the absent tSSEP responses (P=0.002 and P=0.005, respectively). tSSEP score was significantly higher in patients with brainstem lesions (P=0.01), especially midbrain (P=0.004

2016 Croatian medical journal

171. Neural and Response Correlations to Complex Natural Sounds in the Auditory Midbrain Full Text available with Trip Pro

Neural and Response Correlations to Complex Natural Sounds in the Auditory Midbrain How natural communication sounds are spatially represented across the inferior colliculus, the main center of convergence for auditory information in the midbrain, is not known. The neural representation of the acoustic stimuli results from the interplay of locally differing input and the organization of spectral and temporal neural preferences that change gradually across the nucleus. This raises the question

2016 Frontiers in neural circuits

172. Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae Full Text available with Trip Pro

Stathmin-like 4 is critical for the maintenance of neural progenitor cells in dorsal midbrain of zebrafish larvae A delicate balance between proliferating and differentiating signals is necessary to ensure proper growth and neuronal specification. By studying the developing zebrafish brain, we observed a specific and dynamic expression of a microtubule destabilizer gene, stathmin-like 4 (stmn4), in the dorsal midbrain region. The expression of stmn4 was mutually exclusive to a pan-neuronal (...) marker, elavl3 that indicates its role in regulating neurogenesis. We showed the knockdown or overexpression of stmn4 resulted in premature neuronal differentiation in dorsal midbrain. We also generated stmn4 maternal-zygotic knockout zebrafish by the CRISPR/Cas9 system. Unexpectedly, only less than 10% of stmn4 mutants showed similar phenotypes observed in that of stmn4 morphants. It might be due to the complementation of the increased stmn1b expression observed in stmn4 mutants. In addition, time

2016 Scientific reports

173. Midbrain Frequency Representation following Moderately Intense Neonatal Sound Exposure in a Precocious Animal Model (Chinchilla laniger) Full Text available with Trip Pro

Midbrain Frequency Representation following Moderately Intense Neonatal Sound Exposure in a Precocious Animal Model (Chinchilla laniger) Auditory brain areas undergo reorganization resulting from abnormal sensory input during early postnatal development. This is evident from studies at the cortical level but it remains unclear whether there is reorganization in the auditory midbrain in a species similar to the human, that is, with early hearing onset. We have explored midbrain plasticity (...) the exposure frequency at 8 kHz. In addition, we report a significant increase in low frequency representation (<1 kHz), again a change to tonotopic mapping distant to the 2 kHz region. Thus in a precocious species, tonotopic maps in auditory midbrain are altered following abnormal stimulation during development. However, these changes are more complex than the overrepresentation of exposure related frequency regions that are often reported.

2016 Neural plasticity

174. Incorporating Midbrain Adaptation to Mean Sound Level Improves Models of Auditory Cortical Processing Full Text available with Trip Pro

Incorporating Midbrain Adaptation to Mean Sound Level Improves Models of Auditory Cortical Processing Adaptation to stimulus statistics, such as the mean level and contrast of recently heard sounds, has been demonstrated at various levels of the auditory pathway. It allows the nervous system to operate over the wide range of intensities and contrasts found in the natural world. Yet current standard models of the response properties of auditory neurons do not incorporate such adaptation. Here we (...) than the standard LN model for a range of synthetic and natural stimuli. The IC Adaptation model introduces no extra free parameters, so it improves predictions without sacrificing parsimony. Furthermore, the time constants of adaptation in the IC appear to be matched to the statistics of natural sounds, suggesting that neurons in the auditory midbrain predict the mean level of future sounds and adapt their responses appropriately.An ability to accurately predict how sensory neurons respond

2016 The Journal of Neuroscience

175. Socially induced serotonergic fluctuations in the male auditory midbrain correlate with female behavior during courtship Full Text available with Trip Pro

Socially induced serotonergic fluctuations in the male auditory midbrain correlate with female behavior during courtship Cues from social partners trigger the activation of socially responsive neuromodulatory systems, priming brain regions including sensory systems to process these cues appropriately. The fidelity with which neuromodulators reflect the qualities of ongoing social interactions in sensory regions is unclear. We addressed this issue by using voltammetry to monitor serotonergic (...) fluctuations in an auditory midbrain nucleus, the inferior colliculus (IC), of male mice (Mus musculus) paired with females, and by concurrently measuring behaviors of both social partners. Serotonergic activity strongly increased in male mice as they courted females, relative to serotonergic activity in the same males during trials with no social partners. Across individual males, average changes in serotonergic activity were negatively correlated with behaviors exhibited by female partners, including

2016 Journal of neurophysiology

176. Neural correlates of behavioral amplitude modulation sensitivity in the budgerigar midbrain Full Text available with Trip Pro

Neural correlates of behavioral amplitude modulation sensitivity in the budgerigar midbrain Amplitude modulation (AM) is a crucial feature of many communication signals, including speech. Whereas average discharge rates in the auditory midbrain correlate with behavioral AM sensitivity in rabbits, the neural bases of AM sensitivity in species with human-like behavioral acuity are unexplored. Here, we used parallel behavioral and neurophysiological experiments to explore the neural (midbrain (...) ) bases of AM perception in an avian speech mimic, the budgerigar (Melopsittacus undulatus). Behavioral AM sensitivity was quantified using operant conditioning procedures. Neural AM sensitivity was studied using chronically implanted microelectrodes in awake, unrestrained birds. Average discharge rates of multiunit recording sites in the budgerigar midbrain were insufficient to explain behavioral sensitivity to modulation frequencies <100 Hz for both tone- and noise-carrier stimuli, even with optimal

2016 Journal of neurophysiology

177. Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: Link to impulsivity in methamphetamine users Full Text available with Trip Pro

Midbrain functional connectivity and ventral striatal dopamine D2-type receptors: Link to impulsivity in methamphetamine users Stimulant use disorders are associated with deficits in striatal dopamine receptor availability, abnormalities in mesocorticolimbic resting-state functional connectivity (RSFC) and impulsivity. In methamphetamine-dependent research participants, impulsivity is correlated negatively with striatal D2-type receptor availability, and mesocorticolimbic RSFC is stronger than (...) that in controls. The extent to which these features of methamphetamine dependence are interrelated, however, is unknown. This question was addressed in two studies. In Study 1, 19 methamphetamine-dependent and 26 healthy control subjects underwent [18F]fallypride positron emission tomography to measure ventral striatal dopamine D2-type receptor availability, indexed by binding potential (BPND), and functional magnetic resonance imaging (fMRI) to assess mesocorticolimbic RSFC, using a midbrain seed. In Study 2

2016 Molecular psychiatry

178. Specificity and impact of adrenergic projections to the midbrain dopamine system Full Text available with Trip Pro

Specificity and impact of adrenergic projections to the midbrain dopamine system Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson's disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic (...) interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system. This article is part of a Special Issue entitled SI: Noradrenergic System.Copyright ©

2016 Brain research

179. α-Synuclein–induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models Full Text available with Trip Pro

α-Synuclein–induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of protein aggregates comprised of α-synuclein (α-syn). A major barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways capable of reducing aggregates in human neuronal model systems. Mutations in key components of protein (...) trafficking and cellular degradation machinery represent important risk factors for PD; however, their precise role in disease progression and interaction with α-syn remains unclear. Here, we find that α-syn accumulation reduced lysosomal degradation capacity in human midbrain dopamine models of synucleinopathies through disrupting hydrolase trafficking. Accumulation of α-syn at the cell body resulted in aberrant association with cis-Golgi-tethering factor GM130 and disrupted the endoplasmic reticulum

2016 Proceedings of the National Academy of Sciences of the United States of America

180. Microstructure of the Midbrain and Cervical Spinal Cord in Idiopathic Restless Legs Syndrome: A Diffusion Tensor Imaging Study Full Text available with Trip Pro

Microstructure of the Midbrain and Cervical Spinal Cord in Idiopathic Restless Legs Syndrome: A Diffusion Tensor Imaging Study Diffusion tensor imaging (DTI) allows the study of white matter microstructure in the central nervous system. The aim of this study was to examine the DTI metrics of the cervical spinal cord and the brainstem up to the midbrain in patients with idiopathic restless legs (RLS) compared to matched healthy controls.DTI analysis of the cervical spinal cord and the brainstem (...) up into the midbrain was performed in 25 patients with idiopathic RLS and 25 matched healthy controls. Data analysis in the brain was performed by voxelwise comparison of fractional anisotropy (FA) maps at group level. Cervical spinal cord data analysis was performed by slicewise analysis of averaged FA values in axial slices along the spinal cord.Voxelwise comparison of FA maps in the brainstem showed significant microstructural alterations in two clusters in the midbrain bilaterally. Slicewise

2016 Sleep

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