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21. Target‐specific forebrain projections and appropriate synaptic inputs of hESC‐derived dopamine neurons grafted to the midbrain of parkinsonian rats Full Text available with Trip Pro

Target‐specific forebrain projections and appropriate synaptic inputs of hESC‐derived dopamine neurons grafted to the midbrain of parkinsonian rats Dopamine (DA) neurons derived from human embryonic stem cells (hESCs) are a promising unlimited source of cells for cell replacement therapy in Parkinson's disease (PD). A number of studies have demonstrated functionality of DA neurons originating from hESCs when grafted to the striatum of rodent and non-human primate models of PD. However (...) , several questions remain in regard to their axonal outgrowth potential and capacity to integrate into host circuitry. Here, ventral midbrain (VM) patterned hESC-derived progenitors were grafted into the midbrain of 6-hydroxydopamine-lesioned rats, and analyzed at 6, 18, and 24 weeks for a time-course evaluation of specificity and extent of graft-derived fiber outgrowth as well as potential for functional recovery. To investigate synaptic integration of the transplanted cells, we used rabies-based

2018 The Journal of comparative neurology

22. Spatial frequency sensitivity in macaque midbrain Full Text available with Trip Pro

Spatial frequency sensitivity in macaque midbrain Visual brain areas exhibit tuning characteristics well suited for image statistics present in our natural environment. However, visual sensation is an active process, and if there are any brain areas that ought to be particularly in tune with natural scene statistics, it would be sensory-motor areas critical for guiding behavior. Here we found that the rhesus macaque superior colliculus, a structure instrumental for rapid visual exploration

2018 Nature communications

23. The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation Full Text available with Trip Pro

The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation The development of midbrain dopaminergic (mDA) neurons is controlled by multiple morphogens and transcription factors. However, little is known about the role of extracellular matrix proteins in this process. Here we examined the function of roof plate-specific spondins (RSPO1-4) and the floor plate-specific, spondin 1 (SPON1). Only RSPO2 and SPON1 were expressed at high levels during mDA (...) neurogenesis, and the receptor LGR5 was expressed by midbrain floor plate progenitors. Surprisingly, RSPO2, but not SPON1, specifically promoted the differentiation of mDA neuroblasts into mDA neurons in mouse primary cultures and embryonic stem cells (ESCs). In addition, RSPO2 was found to promote not only mDA differentiation, but also mDA neurogenesis in human ESCs. Our results thus uncover an unexpected function of the matricellular protein RSPO2 and suggest an application to improve mDA neurogenesis

2018 Stem cell reports

24. Anatomical Templates of the Midbrain Ventral Tegmental Area and Substantia Nigra for Asian Populations Full Text available with Trip Pro

Anatomical Templates of the Midbrain Ventral Tegmental Area and Substantia Nigra for Asian Populations Increasing evidence shows that the midbrain dopaminergic system is involved in various functions. However, details of the role of the midbrain dopaminergic system in these functions are still to be determined in humans. Considering that the ventral tegmental area (VTA) and substantia nigra (SN) in the midbrain are the primary dopamine producers, creating reliable anatomical templates (...) seeds that were created based on normalized templates from dataset 1. Subsequently, a seed-based functional connectivity analysis was performed using VTA and SN seeds in another, larger sample (dataset 2) to assess whether neural networks of VTA or SN seeds from dataset 1 would be replicated in dataset 2. The Asian VTA template was smaller and located in a more posterior and inferior part of the midbrain compared to the published VTA template, while the Asian SN template, relative to the published

2018 Frontiers in Psychiatry

25. The Use of Physiological Signals in Brainstem/Midbrain fMRI Full Text available with Trip Pro

The Use of Physiological Signals in Brainstem/Midbrain fMRI Brainstem and midbrain nuclei are closely linked to cognitive performance and autonomic function. To advance the localization in this area, precise functional imaging is fundamental. In this study, we used a sophisticated fMRI technique as well as physiological recordings to investigate the involvement of brainstem/midbrain nuclei in cognitive control during a Stroop task. The temporal signal-to-noise ratio (tSNR) increased due (...) to physiological noise correction (PNC) especially in regions adjacent to arteries and cerebrospinal fluid. Within the brainstem/cerebellum template an average tSNR of 68 ± 16 was achieved after the simultaneous application of a high-resolution fMRI, specialized co-registration, and PNC. The analysis of PNC data revealed an activation of the substantia nigra in the Stroop interference contrast whereas no significant results were obtained in the midbrain or brainstem when analyzing uncorrected data

2018 Frontiers in neuroscience

26. Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors Full Text available with Trip Pro

Mesopontine cholinergic inputs to midbrain dopamine neurons drive stress-induced depressive-like behaviors Stressful life events are primary environmental factors that markedly contribute to depression by triggering brain cellular maladaptations. Dysregulation of ventral tegmental area (VTA) dopamine neurons has been causally linked to the appearance of social withdrawal and anhedonia, two classical manifestations of depression. However, the relevant inputs that shape these dopamine signals

2018 Nature communications

27. HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons Full Text available with Trip Pro

HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain dopamine neurons Environmental and genetic risk factors contribute to Parkinson's Disease (PD) pathogenesis and the associated midbrain dopamine (mDA) neuron loss. Here, we identify early PD pathogenic events by developing methodology that utilizes recent innovations in human pluripotent stem cells (hPSC) and chemical sensors of HSP90-incorporating chaperome networks. We show

2018 Nature communications

28. Cortical visual processing evokes short-latency reward-predicting cue responses in primate midbrain dopamine neurons Full Text available with Trip Pro

Cortical visual processing evokes short-latency reward-predicting cue responses in primate midbrain dopamine neurons After classical conditioning dopamine (DA) neurons exhibit short latency responses to reward-predicting visual cues. At least two possible projections could induce such DA responses; the cortical and subcortical visual pathways. Our recent study has shown that after a lesion of the striate cortex (V1), the superior colliculus (SC), a critical node of the subcortical visual

2018 Scientific reports

29. mGluR1-Dependent Long Term Depression in Rodent Midbrain Dopamine Neurons Is Regulated by Neuregulin 1/ErbB Signaling Full Text available with Trip Pro

mGluR1-Dependent Long Term Depression in Rodent Midbrain Dopamine Neurons Is Regulated by Neuregulin 1/ErbB Signaling Increasing evidence demonstrates that the neurotrophic factor Neuregulin 1 (NRG1) and its receptors, ErbB tyrosine kinases, modulate midbrain dopamine (DA) transmission. We have previously reported that NRG1/ErbB signaling is essential for proper metabotropic glutamate receptors 1 (mGluR1) functioning in midbrain DA neurons, thus the functional interaction between ErbB receptors

2018 Frontiers in molecular neuroscience

30. 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. Bilateral medial rectus palsy due to midbrain infarction following concussion head injury Full Text available with Trip Pro

Bilateral medial rectus palsy due to midbrain infarction following concussion head injury Here, we report a rare case of bilateral medial rectus palsy following closed head injury. An adult male had an accidental fall which rendered him unconscious. This was followed by diplopia and restricted ocular motility. He received supportive medical therapy. He was examined for systemic medical and ophthalmic findings. Routine laboratory tests and imaging techniques were employed as per the symptoms (...) . Diffusion-weighted imaging on magnetic resonance imaging proved it to be a rare presentation of small bilateral midbrain infarct. He recovered fully after 8 months.

2018 Indian journal of ophthalmology

37. Bilateral Vertical Gaze Palsy after Cerebral Digital Subtraction Angiography Due to Unilateral Midbrain Infarction Full Text available with Trip Pro

Bilateral Vertical Gaze Palsy after Cerebral Digital Subtraction Angiography Due to Unilateral Midbrain Infarction 29560622 2018 08 10 2018 11 14 2092-9382 32 2 2018 04 Korean journal of ophthalmology : KJO Korean J Ophthalmol Bilateral Vertical Gaze Palsy after Cerebral Digital Subtraction Angiography Due to Unilateral Midbrain Infarction. 154-156 10.3341/kjo.2017.0065 Kim Jong Hoon JH Department of Neurosurgery, Yeungnam University College of Medicine, Daegu, Korea. Kim Won Jae WJ Department

2018 Korean journal of ophthalmology : KJO

38. 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

39. 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

40. Unique case of midbrain tuberculoma presenting as isolated inferior rectus palsy with nystagmus Full Text available with Trip Pro

Unique case of midbrain tuberculoma presenting as isolated inferior rectus palsy with nystagmus Isolated brain stem tuberculoma constitutes about 5% of all intracranial tuberculomas. A case of isolated inferior rectus palsy with downbeat nystagmus due to presumed midbrain tuberculoma in an immunocompetent patient is described here. This report documents a rare entity of a combination of partial third nerve palsy with pupil involvement along with downbeat nystagmus.

2018 Indian journal of ophthalmology

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