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Midbrain

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21. Development of the Mechanisms Governing Midbrain Multisensory Integration Full Text available with Trip Pro

Development of the Mechanisms Governing Midbrain Multisensory Integration The ability to integrate information across multiple senses enhances the brain's ability to detect, localize, and identify external events. This process has been well documented in single neurons in the superior colliculus (SC), which synthesize concordant combinations of visual, auditory, and/or somatosensory signals to enhance the vigor of their responses. This increases the physiological salience of crossmodal events (...) with crossmodal cues is acquired. Recent empirical findings suggest that the mechanisms supporting this development must be more complex than previously believed. The present work integrates these data with what is already known about the underlying circuit in the midbrain to create and test a mechanistic model of multisensory development. This model represents a novel and comprehensive framework that explains how midbrain circuits acquire multisensory experience and reveals how disruptions in this neurotypic

2018 The Journal of Neuroscience

22. Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice Full Text available with Trip Pro

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

23. 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 available with Trip Pro

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

24. miR-182-5p and miR-183-5p Act as GDNF Mimics in Dopaminergic Midbrain Neurons Full Text available with Trip Pro

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

25. BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In Vivo and in Human Induced Pluripotent and Neural Stem Cells Full Text available with Trip Pro

BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic Neurons In Vivo and in Human Induced Pluripotent and Neural Stem Cells The embryonic formation of midbrain dopaminergic (mDA) neurons in vivo provides critical guidelines for the in vitro differentiation of mDA neurons from stem cells, which are currently being developed for Parkinson's disease cell replacement therapy. Bone morphogenetic protein (BMP)/SMAD inhibition is routinely used during early steps of stem cell (...) signaling as a novel essential pathway regulating the development of mammalian midbrain dopaminergic (mDA) neurons in vivo and provide insights into the molecular mechanisms of this process. BMP5/7 regulate MSX1/2 (msh homeobox 1/2) and SHH (sonic hedgehog) expression to direct mDA neurogenesis. Moreover, the BMP signaling component SMAD1 controls the differentiation of mDA progenitors, particularly to substantia nigra neurons, by directing their cell cycle exit. Importantly, BMP5/7 increase robustly

2018 The Journal of Neuroscience

26. Author Correction: Midbrain circuit regulation of individual alcohol drinking behaviors in mice Full Text available with Trip Pro

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

27. Dynamic representation of 3D auditory space in the midbrain of the free-flying echolocating bat Full Text available with Trip Pro

Dynamic representation of 3D auditory space in the midbrain of the free-flying echolocating bat Essential to spatial orientation in the natural environment is a dynamic representation of direction and distance to objects. Despite the importance of 3D spatial localization to parse objects in the environment and to guide movement, most neurophysiological investigations of sensory mapping have been limited to studies of restrained subjects, tested with 2D, artificial stimuli. Here, we show (...) for the first time that sensory neurons in the midbrain superior colliculus (SC) of the free-flying echolocating bat encode 3D egocentric space, and that the bat's inspection of objects in the physical environment sharpens tuning of single neurons, and shifts peak responses to represent closer distances. These findings emerged from wireless neural recordings in free-flying bats, in combination with an echo model that computes the animal's instantaneous stimulus space. Our research reveals dynamic 3D space

2018 eLife

28. Wnt signal activation induces midbrain specification through direct binding of the beta-catenin/TCF4 complex to the EN1 promoter in human pluripotent stem cells Full Text available with Trip Pro

Wnt signal activation induces midbrain specification through direct binding of the beta-catenin/TCF4 complex to the EN1 promoter in human pluripotent stem cells The canonical Wnt signal pathway plays a pivotal role in anteroposterior patterning and midbrain specification during early neurogenesis. Activating Wnt signal has been a strategy for differentiating human pluripotent stem cells (PSCs) into midbrain dopaminergic (DA) neurons; however, the underlying molecular mechanism(s) of how the Wnt (...) signal drives posterior fate remained unclear. In this study, we found that activating the canonical Wnt signal significantly upregulated the expression of EN1, a midbrain-specific marker, in a fibroblast growth factor signal-dependent manner in human PSC-derived neural precursor cells (NPCs). The EN1 promoter region contains a putative TCF4-binding site that directly interacts with the β-catenin/TCF complex upon Wnt signal activation. Once differentiated, NPCs treated with a Wnt signal agonist gave

2018 Experimental & molecular medicine

29. Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics Full Text available with Trip Pro

Cellular diversity in the Drosophila midbrain revealed by single-cell transcriptomics To understand the brain, molecular details need to be overlaid onto neural wiring diagrams so that synaptic mode, neuromodulation and critical signaling operations can be considered. Single-cell transcriptomics provide a unique opportunity to collect this information. Here we present an initial analysis of thousands of individual cells from Drosophila midbrain, that were acquired using Drop-Seq. A number

2018 eLife

30. Identity prediction errors in the human midbrain update reward-identity expectations in the orbitofrontal cortex Full Text available with Trip Pro

Identity prediction errors in the human midbrain update reward-identity expectations in the orbitofrontal cortex There is general consensus that dopaminergic midbrain neurons signal reward prediction errors, computed as the difference between expected and received reward value. However, recent work in rodents shows that these neurons also respond to errors related to inferred value and sensory features, indicating an expanded role for dopamine beyond learning cached values. Here we utilize (...) a transreinforcer reversal learning task and functional magnetic resonance imaging (fMRI) to test whether prediction error signals in the human midbrain are evoked when the expected identity of an appetitive food odor reward is violated, while leaving value matched. We found that midbrain fMRI responses to identity and value errors are correlated, suggesting a common neural origin for these error signals. Moreover, changes in reward-identity expectations, encoded in the orbitofrontal cortex (OFC), are directly

2018 Nature communications

31. Astrocyte Hypertrophy and Microglia Activation in the Rat Auditory Midbrain Is Induced by Electrical Intracochlear Stimulation Full Text available with Trip Pro

Astrocyte Hypertrophy and Microglia Activation in the Rat Auditory Midbrain Is Induced by Electrical Intracochlear Stimulation Neuron-glia interactions contribute to tissue homeostasis and functional plasticity in the mammalian brain, but it remains unclear how this is achieved. The potential of central auditory brain tissue for stimulation-dependent cellular remodeling was studied in hearing-experienced and neonatally deafened rats. At adulthood, both groups received an intracochlear electrode (...) into the left cochlea and were continuously stimulated for 1 or 7 days after waking up from anesthesia. Normal hearing and deafness were assessed by auditory brainstem responses (ABRs). The effectiveness of stimulation was verified by electrically evoked ABRs as well as immunocytochemistry and in situ hybridization for the immediate early gene product Fos on sections through the auditory midbrain containing the inferior colliculus (IC). Whereas hearing-experienced animals showed a tonotopically restricted

2018 Frontiers in cellular neuroscience

32. A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling Full Text available with Trip Pro

A GABAergic cell type in the lateral habenula links hypothalamic homeostatic and midbrain motivation circuits with sex steroid signaling The lateral habenula (LHb) has a key role in integrating a variety of neural circuits associated with reward and aversive behaviors. There is limited information about how the different cell types and neuronal circuits within the LHb coordinate physiological and motivational states. Here, we report a cell type in the medial division of the LHb (LHbM) in male (...) rats that is distinguished by: (1) a molecular signature for GABAergic neurotransmission (Slc32a1/VGAT) and estrogen receptor (Esr1/ERα) expression, at both mRNA and protein levels, as well as the mRNA for vesicular glutamate transporter Slc17a6/VGLUT2, which we term the GABAergic estrogen-receptive neuron (GERN); (2) its axonal projection patterns, identified by in vivo juxtacellular labeling, to both local LHb and to midbrain modulatory systems; and (3) its somatic expression of receptors

2018 Translational psychiatry

33. Sequential Role of SOXB2 Factors in GABAergic Neuron Specification of the Dorsal Midbrain Full Text available with Trip Pro

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

34. Zinc and linoleic acid pre-treatment attenuates biochemical and histological changes in the midbrain of rats with rotenone-induced Parkinsonism Full Text available with Trip Pro

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

35. Circadian and Homeostatic Modulation of Multi-Unit Activity in Midbrain Dopaminergic Structures Full Text available with Trip Pro

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

36. Phasic Stimulation of Midbrain Dopamine Neuron Activity Reduces Salt Consumption Full Text available with Trip Pro

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

37. Optogenetic auditory fMRI reveals the effects of visual cortical inputs on auditory midbrain response Full Text available with Trip Pro

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

38. Midbrain circuits that set locomotor speed and gait selection Full Text available with Trip Pro

Midbrain circuits that set locomotor speed and gait selection Locomotion is a fundamental motor function common to the animal kingdom. It is implemented episodically and adapted to behavioural needs, including exploration, which requires slow locomotion, and escape behaviour, which necessitates faster speeds. The control of these functions originates in brainstem structures, although the neuronal substrate(s) that support them have not yet been elucidated. Here we show in mice that speed (...) and gait selection are controlled by glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). GlutNs in both of these regions contribute to the control of slower, alternating-gait locomotion, whereas only GlutNs in the CnF are able to elicit high-speed, synchronous-gait locomotion. Additionally, both the activation dynamics and the input and output connectivity matrices of GlutNs in the PPN and the CnF

2018 Nature

39. Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons Full Text available with Trip Pro

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

40. Isolated Spontaneous Midbrain Hemorrhage in a 14-Year-Old Boy Full Text available with Trip Pro

Isolated Spontaneous Midbrain Hemorrhage in a 14-Year-Old Boy Isolated spontaneous midbrain hemorrhages are rare because they are usually secondary to hemorrhages from inferior structures such as the pons and cerebellum, or superior structures such as the thalamus and putamen. While the etiologies are largely unidentified, the most common ones are vascular malformations and bleeding diathesis with hypertension being relatively uncommon. We report midbrain hemorrhage in a 14-year-old boy (...) with a long-standing history of frequent migraine headaches and attention deficit/hyperactivity disorder (ADHD). Neurologic examinations, noncontrast computed tomography (CT) scans, and magnetic resonance imaging (MRI) suggested that the lesion likely affected the dorsal part of the midbrain. The neurologic symptoms improved following endoscopic third ventriculostomy (ETV) with the placement of external ventricular drains (EVDs). In this report, anatomical correlations to the case are discussed

2017 Journal of neurological surgery reports

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