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Midbrain

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181. Synchrony, connectivity, and functional similarity in auditory midbrain local circuits Full Text available with Trip Pro

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

2016 Neuroscience

182. Effect of informational content of noise on speech representation in the aging midbrain and cortex Full Text available with Trip Pro

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

2016 Journal of neurophysiology

183. Endocannabinoids control vesicle release mode at midbrain periaqueductal grey inhibitory synapses Full Text available with Trip Pro

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

2016 The Journal of physiology

184. Association of morphine-induced analgesic tolerance with changes in gene expression of GluN1 and MOR1 in rat spinal cord and midbrain Full Text available with Trip Pro

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

2016 Iranian journal of basic medical sciences

185. Repetition suppression in the medial temporal lobe and midbrain is altered by event overlap Full Text available with Trip Pro

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

2016 Hippocampus

186. Ventral Midbrain NMDA Receptor Blockade: From Enhanced Reward and Dopamine Inactivation Full Text available with Trip Pro

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

2016 Frontiers in behavioral neuroscience

187. One more factor joins the plot: Pbx1 regulates differentiation and survival of midbrain dopaminergic neurons Full Text available with Trip Pro

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

2016 The EMBO journal

188. Evidence of degraded representation of speech in noise, in the aging midbrain and cortex Full Text available with Trip Pro

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

2016 Journal of neurophysiology

189. Non-Monotonic Relation between Noise Exposure Severity and Neuronal Hyperactivity in the Auditory Midbrain Full Text available with Trip Pro

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

2016 Frontiers in neurology

190. 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

191. Midbrain Synchrony to Envelope Structure Supports Behavioral Sensitivity to Single-Formant Vowel-Like Sounds in Noise Full Text available with Trip Pro

Midbrain Synchrony to Envelope Structure Supports Behavioral Sensitivity to Single-Formant Vowel-Like Sounds in Noise Vowels make a strong contribution to speech perception under natural conditions. Vowels are encoded in the auditory nerve primarily through neural synchrony to temporal fine structure and to envelope fluctuations rather than through average discharge rate. Neural synchrony is thought to contribute less to vowel coding in central auditory nuclei, consistent with more limited (...) synchronization to fine structure and the emergence of average-rate coding of envelope fluctuations. However, this hypothesis is largely unexplored, especially in background noise. The present study examined coding mechanisms at the level of the midbrain that support behavioral sensitivity to simple vowel-like sounds using neurophysiological recordings and matched behavioral experiments in the budgerigar. Stimuli were harmonic tone complexes with energy concentrated at one spectral peak, or formant frequency

2016 JARO: Journal of the Association for Research in Otolaryngology

192. Definition of a critical spatiotemporal window within which primary cilia control midbrain dopaminergic neurogenesis Full Text available with Trip Pro

Definition of a critical spatiotemporal window within which primary cilia control midbrain dopaminergic neurogenesis Midbrain dopaminergic (mDA) neurons are generated in the ventral midbrain floor plate depending on Sonic Hedgehog (SHH) signaling for induction. Primary cilia transduce canonical SHH signals. Loss of intraflagellar transport protein IFT88, essential for ciliary function, disrupts SHH signaling in the ventral midbrain and results in the reduction in mDA progenitors and neurons. We

2016 Neurogenesis

193. Parkin and PINK1 Patient iPSC-Derived Midbrain Dopamine Neurons Exhibit Mitochondrial Dysfunction and α-Synuclein Accumulation Full Text available with Trip Pro

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

2016 Stem cell reports

194. Midbrain Gene Screening Identifies a New Mesoaccumbal Glutamatergic Pathway and a Marker for Dopamine Cells Neuroprotected in Parkinson’s Disease Full Text available with Trip Pro

Midbrain Gene Screening Identifies a New Mesoaccumbal Glutamatergic Pathway and a Marker for Dopamine Cells Neuroprotected in Parkinson’s Disease The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) of the midbrain are associated with Parkinson's disease (PD), schizophrenia, mood disorders and addiction. Based on the recently unraveled heterogeneity within the VTA and SNc, where glutamate, GABA and co-releasing neurons have been found to co-exist with the classical (...) dopamine neurons, there is a compelling need for identification of gene expression patterns that represent this heterogeneity and that are of value for development of human therapies. Here, several unique gene expression patterns were identified in the mouse midbrain of which NeuroD6 and Grp were expressed within different dopaminergic subpopulations of the VTA, and TrpV1 within a small heterogeneous population. Optogenetics-coupled in vivo amperometry revealed a previously unknown glutamatergic

2016 Scientific reports

195. 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

196. 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

197. 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

198. Midbrain dopamine neurons signal aversion in a reward-context-dependent manner Full Text available with Trip Pro

Midbrain dopamine neurons signal aversion in a reward-context-dependent manner Dopamine is thought to regulate learning from appetitive and aversive events. Here we examined how optogenetically-identified dopamine neurons in the lateral ventral tegmental area of mice respond to aversive events in different conditions. In low reward contexts, most dopamine neurons were exclusively inhibited by aversive events, and expectation reduced dopamine neurons' responses to reward and punishment. When

2016 eLife

199. 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

200. Spatially precise visual gain control mediated by a cholinergic circuit in the midbrain attention network Full Text available with Trip Pro

Spatially precise visual gain control mediated by a cholinergic circuit in the midbrain attention network A primary function of the midbrain stimulus selection network is to compute the highest-priority location for attention and gaze. Here we report the contribution of a specific cholinergic circuit to this computation. We functionally disconnected the tegmental cholinergic nucleus isthmi pars parvocellularis (Ipc) from the optic tectum (OT) in barn owls by reversibly blocking excitatory

2016 Nature communications

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