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Midbrain

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101. Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation Full Text available with Trip Pro

Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation (...) are less clear. Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limit midbrain dopaminergic axon growth and target innervation. Zeb2 levels are downregulated in the embryonic rodent midbrain during the period of dopaminergic axon growth, when BMP pathway components are upregulated. Experimental knockdown of Zeb2 leads to an increase in BMP-Smad-dependent axon growth. Consequently there is dopaminergic hyperinnervation of the striatum, without an increase

2017 Scientific reports

102. Treatment Associated Changes of Functional Connectivity of Midbrain/Brainstem Nuclei in Major Depressive Disorder Full Text available with Trip Pro

Treatment Associated Changes of Functional Connectivity of Midbrain/Brainstem Nuclei in Major Depressive Disorder Previous functional magnetic resonance imaging (fMRI) studies demonstrated an abnormally coordinated network functioning in Major Depression Disorder (MDD) during rest. The main monoamine-producing nuclei within midbrain/brainstem are functionally integrated within these specific networks. Therefore, we aimed to investigate the resting-state functional connectivity (RSFC (...) activation in MDD. The observed differences in the FC of the midbrain/brainstem nuclei between two classes of antidepressants suggest differential neural effects of SSRIs and SNRIs.

2017 Scientific reports

103. Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways Full Text available with Trip Pro

Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways Abnormal development of ventral midbrain (VM) dopaminergic (DA) pathways, essential for motor and cognitive function, may underpin a number of neurological disorders and thereby highlight the importance of understanding the birth and connectivity of the associated neurons. While a number of regulators of VM DA neurogenesis are known, processes involved in later

2017 Scientific reports

104. Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations Full Text available with Trip Pro

Dopamine Induces Oscillatory Activities in Human Midbrain Neurons with Parkin Mutations Locomotor symptoms in Parkinson's disease (PD) are accompanied by widespread oscillatory neuronal activities in basal ganglia. Here, we show that activation of dopamine D1-class receptors elicits a large rhythmic bursting of spontaneous excitatory postsynaptic currents (sEPSCs) in midbrain neurons differentiated from induced pluripotent stem cells (iPSCs) of PD patients with parkin mutations, but not normal (...) in patient-specific iPSC-derived midbrain neurons provides a mechanistic clue to PD pathophysiology, and it demonstrates the usefulness of this model system in understanding how mutations of parkin cause movement symptoms in Parkinson's disease.Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

2017 Cell reports

105. Long-Term Impairment of Sound Processing in the Auditory Midbrain by Daily Short-Term Exposure to Moderate Noise Full Text available with Trip Pro

Long-Term Impairment of Sound Processing in the Auditory Midbrain by Daily Short-Term Exposure to Moderate Noise Most citizen people are exposed daily to environmental noise at moderate levels with a short duration. The aim of the present study was to determine the effects of daily short-term exposure to moderate noise on sound level processing in the auditory midbrain. Sound processing properties of auditory midbrain neurons were recorded in anesthetized mice exposed to moderate noise (80 dB (...) a 12-week period of recovery in a quiet laboratory environment after completion of noise exposure. In conclusion, even daily short-term exposure to moderate noise can cause long-term impairment of sound level processing in a frequency-specific manner in auditory midbrain neurons.

2017 Neural plasticity

106. The noble gas xenon provides protection and trophic stimulation to midbrain dopamine neurons Full Text available with Trip Pro

The noble gas xenon provides protection and trophic stimulation to midbrain dopamine neurons Despite its low chemical reactivity, the noble gas xenon possesses a remarkable spectrum of biological effects. In particular, xenon is a strong neuroprotectant in preclinical models of hypoxic-ischemic brain injury. In this study, we wished to determine whether xenon retained its neuroprotective potential in experimental settings that model the progressive loss of midbrain dopamine (DA) neurons (...) in Parkinson's disease. Using rat midbrain cultures, we established that xenon was partially protective for DA neurons through either direct or indirect effects on these neurons. So, when DA neurons were exposed to l-trans-pyrrolidine-2,4-dicarboxylic acid so as to increase ambient glutamate levels and generate slow and sustained excitotoxicity, the effect of xenon on DA neurons was direct. The vitamin E analog Trolox also partially rescued DA neurons in this setting and enhanced neuroprotection by xenon

2017 Journal of neurochemistry

107. A spiking neural network model of the midbrain superior colliculus that generates saccadic motor commands Full Text available with Trip Pro

A spiking neural network model of the midbrain superior colliculus that generates saccadic motor commands Single-unit recordings suggest that the midbrain superior colliculus (SC) acts as an optimal controller for saccadic gaze shifts. The SC is proposed to be the site within the visuomotor system where the nonlinear spatial-to-temporal transformation is carried out: the population encodes the intended saccade vector by its location in the motor map (spatial), and its trajectory and velocity

2017 Biological cybernetics

108. Ischemic Stroke of Midbrain and Cerebellum Involving Reticular Activating System Full Text available with Trip Pro

Ischemic Stroke of Midbrain and Cerebellum Involving Reticular Activating System The reticular activating system is the part of the brain that maintains the sleep/wake cycle. Any damage to this region can cause hypersomnolence and drowsiness along with altered sensorium. This case presents a patient with cerebellar and midbrain stroke with infarct of the reticular activating system, leading to hypersomnolence, drowsiness, and altered sensorium.

2017 Cureus

109. OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH ALTERED MIDBRAIN CHEMICAL CONCENTRATIONS Full Text available with Trip Pro

OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH ALTERED MIDBRAIN CHEMICAL CONCENTRATIONS Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic (...) resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting

2017 Neuroscience

110. LOSS OF HYPERDIRECT PATHWAY CORTICO-SUBTHALAMIC INPUTS FOLLOWING DEGENERATION OF MIDBRAIN DOPAMINE NEURONS Full Text available with Trip Pro

LOSS OF HYPERDIRECT PATHWAY CORTICO-SUBTHALAMIC INPUTS FOLLOWING DEGENERATION OF MIDBRAIN DOPAMINE NEURONS The motor symptoms of Parkinson's disease (PD) are linked to abnormally correlated and coherent activity in the cortex and subthalamic nucleus (STN). However, in parkinsonian mice we found that cortico-STN transmission strength had diminished by 50%-75% through loss of axo-dendritic and axo-spinous synapses, was incapable of long-term potentiation, and less effectively patterned STN

2017 Neuron

111. Corelease of Inhibitory Neurotransmitters in the Mouse Auditory Midbrain Full Text available with Trip Pro

Corelease of Inhibitory Neurotransmitters in the Mouse Auditory Midbrain The central nucleus of the inferior colliculus (ICC) of the auditory midbrain, which integrates most ascending auditory information from lower brainstem regions, receives prominent long-range inhibitory input from the ventral nucleus of the lateral lemniscus (VNLL), a region thought to be important for temporal pattern discrimination. Histological evidence suggests that neurons in the VNLL release both glycine and GABA (...) receptor subtypes subserving inhibition may offer diverse mechanisms for maintaining inhibitory homeostasis.SIGNIFICANCE STATEMENT Corelease of neurotransmitters is a common feature of the brain. GABA and glycine corelease is particularly common in the spinal cord and brainstem, but its presence in the midbrain is unknown. We show corelease of GABA and glycine for the first time in the central nucleus of the inferior colliculus of the auditory midbrain. Glycine and GABA are both inhibitory

2017 The Journal of Neuroscience

112. Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease Full Text available with Trip Pro

Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease Cultured neural stem/precursor cells (NSCs) are regarded as a potential systematic cell source to treat Parkinson's disease (PD). However, the therapeutic potential of these cultured NSCs is lost during culturing. Here, we show that treatment of vitamin C (VC) enhances generation of authentic midbrain-type dopamine (mDA) neurons with improved (...) survival and functions from ventral midbrain (VM)-derived NSCs. VC acted by upregulating a series of mDA neuron-specific developmental and phenotype genes via removal of DNA methylation and repressive histone code (H3K9m3, H3K27m3) at associated gene promoter regions. Notably, the epigenetic changes induced by transient VC treatment were sustained long after VC withdrawal. Accordingly, transplantation of VC-treated NSCs resulted in improved behavioral restoration, along with enriched DA neuron

2017 Stem cell reports

113. 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

Altered activation and connectivity in a hippocampal–basal ganglia–midbrain circuit during salience processing in subjects at ultra high risk for psychosis Animal models of psychosis propose that abnormal hippocampal activity drives increased subcortical dopamine function, which is thought to contribute to aberrant salience processing and psychotic symptoms. These effects appear to be mediated through connections between the hippocampus, ventral striatum/pallidum and the midbrain. The aim (...) of the present study was to examine the activity and connectivity in this pathway in people at ultra high risk (UHR) for psychosis. Functional magnetic resonance imaging was used to compare neural responses in a hippocampal-basal ganglia-midbrain network during reward, novelty and aversion processing between 29 UHR subjects and 32 healthy controls. We then investigated whether effective connectivity within this network is perturbed in UHR subjects, using dynamic causal modelling (DCM). Finally, we examined

2017 Translational psychiatry

114. Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of Chd7 from the Embryonic Mid-Hindbrain Region Full Text available with Trip Pro

Cerebellar Vermis and Midbrain Hypoplasia Upon Conditional Deletion of Chd7 from the Embryonic Mid-Hindbrain Region Reduced fibroblast growth factor (FGF) signaling from the mid-hindbrain or isthmus organizer (IsO) during early embryonic development results in hypoplasia of the midbrain and cerebellar vermis. We previously reported evidence for reduced Fgf8 expression and FGF signaling in the mid-hindbrain region of embryos heterozygous for Chd7, the gene mutated in CHARGE (Coloboma, Heart (...) defects, choanal Atresia, Retarded growth and development, Genitourinary anomalies and Ear defects) syndrome. However, Chd7+/- animals only exhibit mild cerebellar vermis anomalies. As homozygous deletion of Chd7 is embryonic lethal, we conditionally deleted Chd7 from the early embryonic mid-hindbrain region to identify the function of CHD7 in mid-hindbrain development. Using a combination of high resolution structural MRI and histology, we report striking midbrain and cerebellar vermis hypoplasia

2017 Frontiers in neuroanatomy

115. VMAT2-Mediated Neurotransmission from Midbrain Leptin Receptor Neurons in Feeding Regulation Full Text available with Trip Pro

VMAT2-Mediated Neurotransmission from Midbrain Leptin Receptor Neurons in Feeding Regulation Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear. Here, we showed that midbrain LepR neurons overlap with a subset of dopaminergic, GABAergic (...) and glutamatergic neurons. Specific removal of vesicular monoamine transporter 2 (VMAT2) in midbrain LepR neurons (KO mice) disrupted DA accumulation in vesicles, but failed to cause a significant change in the evoked release of either glutamate or GABA to downstream neurons. While KO mice showed no differences on chow, they presented a reduced high-fat diet (HFD) intake and resisted to HFD-induced obesity. Specific activation of midbrain LepR neurons promoted VMAT2-dependent feeding on chow and HFD. When

2017 eNeuro

116. Spatial Processing Is Frequency Specific in Auditory Cortex But Not in the Midbrain Full Text available with Trip Pro

Spatial Processing Is Frequency Specific in Auditory Cortex But Not in the Midbrain The cochlea behaves like a bank of band-pass filters, segregating information into different frequency channels. Some aspects of perception reflect processing within individual channels, but others involve the integration of information across them. One instance of this is sound localization, which improves with increasing bandwidth. The processing of binaural cues for sound location has been studied extensively

2017 The Journal of Neuroscience

117. Neuronal Subset-Specific Migration and Axonal Wiring Mechanisms in the Developing Midbrain Dopamine System Full Text available with Trip Pro

Neuronal Subset-Specific Migration and Axonal Wiring Mechanisms in the Developing Midbrain Dopamine System The midbrain dopamine (mDA) system is involved in the control of cognitive and motor behaviors, and is associated with several psychiatric and neurodegenerative diseases. mDA neurons receive diverse afferent inputs and establish efferent connections with many brain areas. Recent studies have unveiled a high level of molecular and cellular heterogeneity within the mDA system with specific

2017 Frontiers in neuroanatomy

118. Calcium-activated SK channels control firing regularity by modulating sodium channel availability in midbrain dopamine neurons Full Text available with Trip Pro

Calcium-activated SK channels control firing regularity by modulating sodium channel availability in midbrain dopamine neurons Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area regulate behaviours such as reward-related learning, and motor control. Dysfunction of these neurons is implicated in Schizophrenia, addiction to drugs, and Parkinson's disease. While some dopamine neurons fire single spikes at regular intervals, others fire irregular single spikes

2017 Scientific reports

119. Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential Full Text available with Trip Pro

Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use (...) of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked. We demonstrate that expanded mFPPs have increased DA neuron potential and differentiate more efficiently and rapidly than progenitors generated by standard protocols. In addition

2017 Scientific reports

120. Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation Full Text available with Trip Pro

Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means (...) of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC

2017 PLoS genetics

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