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Midbrain

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141. Repetition suppression in the medial temporal lobe and midbrain is altered by event overlap (PubMed)

Repetition suppression in the medial temporal lobe and midbrain is altered by event overlap Repeated encounters with the same event typically lead to decreased activation in the medial temporal lobe (MTL) and dopaminergic midbrain, a phenomenon known as repetition suppression. In contrast, encountering an event that overlaps with prior experience leads to increased response in the same regions. Such increased responding is thought to reflect an associative novelty signal that promotes memory (...) updating to resolve differences between current events and stored memories. Here, we married these ideas to test whether event overlap significantly modulates MTL and midbrain responses-even when events are repeated and expected-to promote memory updating through integration. While undergoing high-resolution functional MRI, participants were repeatedly presented with objects pairs, some of which overlapped with other, intervening pairs and some of which contained elements unique from other pairs. MTL

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2016 Hippocampus

142. Synchrony, connectivity, and functional similarity in auditory midbrain local circuits (PubMed)

Synchrony, connectivity, and functional similarity in auditory midbrain local circuits The central nucleus of the inferior colliculus (ICC) contains a laminar structure that functions as an organizing substrate of ascending inputs and local processing. While topographic distributions of ICC response parameters within and across laminae have been reported, the functional micro-organization of the ICC is less well understood. For pairs of neighboring ICC neurons, we examined the nature

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2016 Neuroscience

143. Evidence of degraded representation of speech in noise, in the aging midbrain and cortex (PubMed)

Evidence of degraded representation of speech in noise, in the aging midbrain and cortex Humans have a remarkable ability to track and understand speech in unfavorable conditions, such as in background noise, but speech understanding in noise does deteriorate with age. Results from several studies have shown that in younger adults, low-frequency auditory cortical activity reliably synchronizes to the speech envelope, even when the background noise is considerably louder than the speech signal (...) . However, cortical speech processing may be limited by age-related decreases in the precision of neural synchronization in the midbrain. To understand better the neural mechanisms contributing to impaired speech perception in older adults, we investigated how aging affects midbrain and cortical encoding of speech when presented in quiet and in the presence of a single-competing talker. Our results suggest that central auditory temporal processing deficits in older adults manifest in both the midbrain

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2016 Journal of neurophysiology

144. One more factor joins the plot: Pbx1 regulates differentiation and survival of midbrain dopaminergic neurons (PubMed)

One more factor joins the plot: Pbx1 regulates differentiation and survival of midbrain dopaminergic neurons 27534772 2018 01 08 2018 12 02 1460-2075 35 18 2016 09 15 The EMBO journal EMBO J. One more factor joins the plot: Pbx1 regulates differentiation and survival of midbrain dopaminergic neurons. 1957-9 10.15252/embj.201695353 Castro Diogo S DS 0000-0001-8178-9565 Molecular Neurobiology Laboratory, Instituto Gulbenkian de Ciência, Oeiras, Portugal. eng Journal Article Comment 2016 08 17

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2016 The EMBO journal

145. Effect of informational content of noise on speech representation in the aging midbrain and cortex (PubMed)

Effect of informational content of noise on speech representation in the aging midbrain and cortex The ability to understand speech is significantly degraded by aging, particularly in noisy environments. One way that older adults cope with this hearing difficulty is through the use of contextual cues. Several behavioral studies have shown that older adults are better at following a conversation when the target speech signal has high contextual content or when the background distractor (...) is not meaningful. Specifically, older adults gain significant benefit in focusing on and understanding speech if the background is spoken by a talker in a language that is not comprehensible to them (i.e., a foreign language). To understand better the neural mechanisms underlying this benefit in older adults, we investigated aging effects on midbrain and cortical encoding of speech when in the presence of a single competing talker speaking in a language that is meaningful or meaningless to the listener (i.e

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2016 Journal of neurophysiology

146. Association of morphine-induced analgesic tolerance with changes in gene expression of GluN1 and MOR1 in rat spinal cord and midbrain (PubMed)

Association of morphine-induced analgesic tolerance with changes in gene expression of GluN1 and MOR1 in rat spinal cord and midbrain We aimed to examine association of gene expression of MOR1 and GluN1 at mRNA level in the lumbosacral cord and midbrain with morphine tolerance in male Wistar rats.Analgesic effects of morphine administrated intraperitoneally at doses of 0.1, 1, 5 and 10 mg/kg were examined using a hot plate test in rats with and without a history of 15 days morphine (10 mg/kg (...) ) treatment. Morphine-induced analgesic tolerance was also assessed on days 1, 5, 10 and 15 of chronic morphine injections. Two groups with history of 15 days injections of saline or morphine (10 mg/kg) were decapitated on day 15 and their lumbosacral cord and midbrain were dissected for evaluating MOR1 and GluN1 gene expression.The results of the hot plate test showed that morphine (5 and 10 mg/kg) induced significant analgesia in naïve rats but its analgesic effects in rats receiving 15 days injections

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2016 Iranian journal of basic medical sciences

147. Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine Inactivation (PubMed)

Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine Inactivation Glutamate stimulates ventral midbrain (VM) N-Methyl-D-Aspartate receptors (NMDAR) to initiate dopamine (DA) burst firing activity, a mode of discharge associated with enhanced DA release and reward. Blockade of VM NMDAR, however, enhances brain stimulation reward (BSR), the results can be explained by a reduction in the inhibitory drive on DA neurons that is also under the control of glutamate. In this study

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2016 Frontiers in behavioral neuroscience

148. Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain (PubMed)

Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain The occurrence of tinnitus can be linked to hearing loss in the majority of cases, but there is nevertheless a large degree of unexplained heterogeneity in the relation between hearing loss and tinnitus. Part of the problem might be that hearing loss is usually quantified in terms of increased hearing thresholds, which only provides limited information about the underlying cochlear damage (...) to octave-band noise at 100 and 105 dB SPL to generate HHL and permanent increases of hearing thresholds, respectively. Deafferentation of ANFs was confirmed through measurement of auditory brainstem responses and cochlear immunohistochemistry. Acute extracellular recordings from the auditory midbrain (inferior colliculus) demonstrated increases in spontaneous neuronal activity (a putative neural correlate of tinnitus) in both groups. Surprisingly, the increase in spontaneous activity was most

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2016 Frontiers in neurology

149. Development and Dynamic Regulation of Mitochondrial Network in Human Midbrain Dopaminergic Neurons Differentiated from iPSCs (PubMed)

Development and Dynamic Regulation of Mitochondrial Network in Human Midbrain Dopaminergic Neurons Differentiated from iPSCs Mitochondria are critical to neurogenesis, but the mechanisms of mitochondria in neurogenesis have not been well explored. We fully characterized mitochondrial alterations and function in relation to the development of human induced pluripotent stem cell (hiPSC)-derived dopaminergic (DA) neurons. Following directed differentiation of hiPSCs to DA neurons, mitochondria

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2016 Stem cell reports

150. Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and α-Synuclein Accumulation (PubMed)

Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and α-Synuclein Accumulation Parkinson's disease (PD) is characterized by the selective loss of dopamine neurons in the substantia nigra; however, the mechanism of neurodegeneration in PD remains unclear. A subset of familial PD is linked to mutations in PARK2 and PINK1, which lead to dysfunctional mitochondria-related proteins Parkin and PINK1, suggesting that pathways implicated (...) in these monogenic forms could play a more general role in PD. We demonstrate that the identification of disease-related phenotypes in PD-patient-specific induced pluripotent stem cell (iPSC)-derived midbrain dopamine (mDA) neurons depends on the type of differentiation protocol utilized. In a floor-plate-based but not a neural-rosette-based directed differentiation strategy, iPSC-derived mDA neurons recapitulate PD phenotypes, including pathogenic protein accumulation, cell-type-specific vulnerability

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2016 Stem cell reports

151. Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses (PubMed)

Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses The midbrain periaqueductal grey (PAG) forms part of an endogenous analgesic system which is tightly regulated by the neurotransmitter GABA. The role of endocannabinoids in regulating GABAergic control of this system was examined in rat PAG slices. Under basal conditions GABAergic neurotransmission onto PAG output neurons was multivesicular. Activation of the endocannabinoid system reduced (...) GABAergic inhibition by reducing the probability of release and by shifting release to a univesicular mode. Blockade of endocannabinoid system unmasked a tonic control over the probability and mode of GABA release. These findings provides a mechanistic foundation for the control of the PAG analgesic system by disinhibition.The midbrain periaqueductal grey (PAG) has a crucial role in coordinating endogenous analgesic responses to physiological and psychological stressors. Endocannabinoids are thought

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2016 The Journal of physiology

152. Cholinergic Mesopontine Signals Govern Locomotion and Reward Through Dissociable Midbrain Pathways (PubMed)

Cholinergic Mesopontine Signals Govern Locomotion and Reward Through Dissociable Midbrain Pathways The mesopontine tegmentum, including the pedunculopontine and laterodorsal tegmental nuclei (PPN and LDT), provides major cholinergic inputs to midbrain and regulates locomotion and reward. To delineate the underlying projection-specific circuit mechanisms, we employed optogenetics to control mesopontine cholinergic neurons at somata and at divergent projections within distinct midbrain areas

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2016 Neuron

153. Reward and choice encoding in terminals of midbrain dopamine neurons depends on striatal target (PubMed)

Reward and choice encoding in terminals of midbrain dopamine neurons depends on striatal target Dopaminergic (DA) neurons in the midbrain provide rich topographic innervation of the striatum and are central to learning and to generating actions. Despite the importance of this DA innervation, it remains unclear whether and how DA neurons are specialized on the basis of the location of their striatal target. Thus, we sought to compare the function of subpopulations of DA neurons that target

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2016 Nature neuroscience

154. Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant (PubMed)

Effects of Electrical Stimulation in the Inferior Colliculus on Frequency Discrimination by Rhesus Monkeys and Implications for the Auditory Midbrain Implant Understanding the relationship between the auditory selectivity of neurons and their contribution to perception is critical to the design of effective auditory brain prosthetics. These prosthetics seek to mimic natural activity patterns to achieve desired perceptual outcomes. We measured the contribution of inferior colliculus (IC) sites (...) for the auditory midbrain implant suggested by our findings is to increase the number and spatial extent of electrodes, to increase the size of the region that can be electrically activated, and to provide a greater range of evoked percepts.Patients with hearing loss stemming from causes that interrupt the auditory pathway after the cochlea need a brain prosthetic to restore hearing. Recently, prosthetic stimulation in the human inferior colliculus (IC) was evaluated in a clinical trial. Thus far, speech

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2016 The Journal of Neuroscience

155. Ldb1 Is Essential for the Development of Isthmic Organizer and Midbrain Dopaminergic Neurons (PubMed)

Ldb1 Is Essential for the Development of Isthmic Organizer and Midbrain Dopaminergic Neurons LIM domain-binding protein 1 (Ldb1) is a nuclear cofactor that interacts with LIM homeodomain proteins to form multiprotein complexes that are important for transcription regulation. Ldb1 has been shown to play essential roles in various processes during mouse embryogenesis. To determine the role of Ldb1 in mid- and hindbrain development, we have generated a conditional mutant with a specific deletion (...) of the Ldb1 in the Engrailed-1-expressing region of the developing mid- and hindbrain. Our study showed that the deletion impaired the expression of signaling molecules, such as fibroblast growth factor 8 (FGF8) and Wnt1, in the isthmic organizer and the expression of Shh in the ventral midbrain. The midbrain and the cerebellum were severely reduced in size, and the midbrain dopaminergic (mDA) neurons were missing in the mutant. These defects are identical to the phenotype that has been observed

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2016 Stem cells and development

156. D-serine in the midbrain periaqueductal gray contributes to morphine tolerance in rats (PubMed)

D-serine in the midbrain periaqueductal gray contributes to morphine tolerance in rats The N-methyl-D-aspartate subtype of glutamate receptor plays a critical role in morphine tolerance. D-serine, a co-agonist of N-methyl-D-aspartate receptor, participates in many physiological and pathophysiological processes via regulating N-methyl-D-aspartate receptor activation. The purinergic P2X7 receptor activation can induce the D-serine release in the central nervous system. This study aimed (...) to investigate the role of the ventrolateral midbrain periaqueductal gray D-serine in the mechanism of morphine tolerance in rats. The development of morphine tolerance was induced in normal adult male Sprague-Dawley rats through subcutaneous injection of morphine (10 mg/kg). The analgesic effect of morphine (5 mg/kg, i.p.) was assessed by measuring mechanical withdrawal thresholds in rats with an electronic von Frey anesthesiometer. The D-serine concentration and serine racemase expression levels

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2016 Molecular pain

157. Convergence‐Retraction Nystagmus Associated with Dorsal Midbrain Lesions in Three Dogs (PubMed)

Convergence‐Retraction Nystagmus Associated with Dorsal Midbrain Lesions in Three Dogs 27169871 2017 05 30 2018 11 13 1939-1676 30 4 2016 Jul Journal of veterinary internal medicine J. Vet. Intern. Med. Convergence-Retraction Nystagmus Associated with Dorsal Midbrain Lesions in Three Dogs. 1229-34 10.1111/jvim.13966 Crawford A H AH Clinical Science and Services, Royal Veterinary College, University of London, Hatfield, Herts, UK. Beltran E E Clinical Science and Services, Royal Veterinary

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2016 Journal of Veterinary Internal Medicine

158. SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation (PubMed)

SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation Searching for new regulators of autophagy involved in selective dopaminergic (DA) neuron loss is a hallmark in the pathogenesis of Parkinson disease (PD). We here report that an endoplasmic reticulum (ER)-associated transmembrane protein SLC35D3 is selectively expressed in subsets of midbrain DA neurons in about 10% TH (tyrosine hydroxylase)-positive neurons in the substantia

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2016 Autophagy

159. Purification of functional human ES and iPSC-derived midbrain dopaminergic progenitors using LRTM1 (PubMed)

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

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2016 Nature communications

160. Molecular Diversity of Midbrain Development in Mouse, Human, and Stem Cells (PubMed)

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.

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2016 Cell

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