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Midbrain

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81. A novel floor plate boundary defined by adjacent En1 and Dbx1 microdomains distinguishes midbrain dopamine and hypothalamic neurons Full Text available with Trip Pro

A novel floor plate boundary defined by adjacent En1 and Dbx1 microdomains distinguishes midbrain dopamine and hypothalamic neurons The mesodiencephalic floor plate (mdFP) is the source of diverse neuron types. Yet, how this structure is compartmentalized has not been clearly elucidated. Here, we identify a novel boundary subdividing the mdFP into two microdomains, defined by engrailed 1 (En1) and developing brain homeobox 1 (Dbx1). Utilizing simultaneous dual and intersectional fate mapping

2017 Development (Cambridge, England)

82. Survival of a Novel Subset of Midbrain Dopaminergic Neurons Projecting to the Lateral Septum Is Dependent on NeuroD Proteins Full Text available with Trip Pro

Survival of a Novel Subset of Midbrain Dopaminergic Neurons Projecting to the Lateral Septum Is Dependent on NeuroD Proteins Midbrain dopaminergic neurons are highly heterogeneous. They differ in their connectivity and firing patterns and, therefore, in their functional properties. The molecular underpinnings of this heterogeneity are largely unknown, and there is a paucity of markers that distinguish these functional subsets. In this paper, we report the identification and characterization (...) of a novel subset of midbrain dopaminergic neurons located in the ventral tegmental area that expresses the basic helix-loop-helix transcription factor, Neurogenic Differentiation Factor-6 (NEUROD6). Retrograde fluorogold tracing experiments demonstrate that Neurod6+ midbrain dopaminergic neurons neurons project to two distinct septal regions: the dorsal and intermediate region of the lateral septum. Loss-of-function studies in mice demonstrate that Neurod6 and the closely related family member Neurod1

2017 The Journal of Neuroscience

83. Cell-autonomous excitation of midbrain dopamine neurons by endocannabinoid-dependent lipid signaling Full Text available with Trip Pro

Cell-autonomous excitation of midbrain dopamine neurons by endocannabinoid-dependent lipid signaling The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons

2017 Neuron

84. In vitro generation of mature midbrain-type dopamine neurons by adjusting exogenous Nurr1 and Foxa2 expressions to their physiologic patterns Full Text available with Trip Pro

In vitro generation of mature midbrain-type dopamine neurons by adjusting exogenous Nurr1 and Foxa2 expressions to their physiologic patterns Developmental information aids stem cell biologists in producing tissue-specific cells. Recapitulation of the developmental profile of a specific cell type in an in vitro stem cell system provides a strategy for manipulating cell-fate choice during the differentiation process. Nurr1 and Foxa2 are potential candidates for genetic engineering to generate (...) midbrain-type dopamine (DA) neurons for experimental and therapeutic applications in Parkinson's disease (PD), as forced expression of these genes in neural stem/precursor cells (NPCs) yields cells with a complete battery of midbrain DA neuron-specific genes. However, simple overexpression without considering their expression pattern in the developing midbrain tends to generate DA cells without adequate neuronal maturation and long-term maintenance of their phenotype in vitro and in vivo after

2017 Experimental & molecular medicine

85. Midbrain dopamine neurons signal belief in choice accuracy during a perceptual decision Full Text available with Trip Pro

Midbrain dopamine neurons signal belief in choice accuracy during a perceptual decision Central to the organization of behavior is the ability to predict the values of outcomes to guide choices. The accuracy of such predictions is honed by a teaching signal that indicates how incorrect a prediction was ("reward prediction error," RPE). In several reinforcement learning contexts, such as Pavlovian conditioning and decisions guided by reward history, this RPE signal is provided by midbrain

2017 Current biology : CB

86. Hierarchical prediction errors in midbrain and septum during social learning Full Text available with Trip Pro

Hierarchical prediction errors in midbrain and septum during social learning Social learning is fundamental to human interactions, yet its computational and physiological mechanisms are not well understood. One prominent open question concerns the role of neuromodulatory transmitters. We combined fMRI, computational modelling and genetics to address this question in two separate samples (N = 35, N = 47). Participants played a game requiring inference on an adviser's intentions whose motivation (...) to help or mislead changed over time. Our analyses suggest that hierarchically structured belief updates about current advice validity and the adviser's trustworthiness, respectively, depend on different neuromodulatory systems. Low-level prediction errors (PEs) about advice accuracy not only activated regions known to support 'theory of mind', but also the dopaminergic midbrain. Furthermore, PE responses in ventral striatum were influenced by the Met/Val polymorphism of the Catechol-O

2017 Social cognitive and affective neuroscience

87. Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly Full Text available with Trip Pro

Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly Motivation can have invigorating effects on behavior via dopaminergic neuromodulation. While this relationship has mainly been established in theoretical models and studies in younger subjects, the impact of structural declines of the dopaminergic system during healthy aging remains unclear. To investigate this issue, we used electroencephalography (EEG) in healthy

2017 Frontiers in aging neuroscience

88. Roundabout receptor 2 maintains inhibitory control of the adult midbrain Full Text available with Trip Pro

Roundabout receptor 2 maintains inhibitory control of the adult midbrain The maintenance of excitatory and inhibitory balance in the brain is essential for its function. Here we find that the developmental axon guidance receptor Roundabout 2 (Robo2) is critical for the maintenance of inhibitory synapses in the adult ventral tegmental area (VTA), a brain region important for the production of the neurotransmitter dopamine. Following selective genetic inactivation of Robo2 in the adult VTA

2017 eLife

89. Gene Expression Profiling with Cre-Conditional Pseudorabies Virus Reveals a Subset of Midbrain Neurons That Participate in Reward Circuitry Full Text available with Trip Pro

Gene Expression Profiling with Cre-Conditional Pseudorabies Virus Reveals a Subset of Midbrain Neurons That Participate in Reward Circuitry The mesolimbic dopamine pathway receives inputs from numerous regions of the brain as part of a neural system that detects rewarding stimuli and coordinates a behavioral response. The capacity to simultaneously map and molecularly define the components of this complex multisynaptic circuit would thus advance our understanding of the determinants

2017 The Journal of Neuroscience

90. Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells Full Text available with Trip Pro

Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups (...) of dopaminergic neurons, which make them an attractive model for the study of Parkinson's disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we show the presence of synaptic connections and electrophysiological activity. The complexity of this model is further highlighted by the myelination of neurites. The present midbrain organoid system has the potential to be used for advanced in vitro disease modeling and therapy

2017 Stem cell reports

91. Targeting transcriptional regulators to regenerate midbrain dopaminergic axons in Parkinson's disease Full Text available with Trip Pro

Targeting transcriptional regulators to regenerate midbrain dopaminergic axons in Parkinson's disease 29239326 2018 11 13 1673-5374 12 11 2017 Nov Neural regeneration research Neural Regen Res Targeting transcriptional regulators to regenerate midbrain dopaminergic axons in Parkinson's disease. 1814-1815 10.4103/1673-5374.219039 Hegarty Shane V SV Department of Anatomy and Neuroscience, Western Gateway Building, University College Cork, Cork, Ireland. Sullivan Aideen M AM Department of Anatomy

2017 Neural Regeneration Research

92. Tcf12 Is Involved in Early Cell-Fate Determination and Subset Specification of Midbrain Dopamine Neurons Full Text available with Trip Pro

Tcf12 Is Involved in Early Cell-Fate Determination and Subset Specification of Midbrain Dopamine Neurons The basic helix-loop-helix (bHLH) protein family has previously been shown to be involved in the development of mesodiencephalic dopaminergic (mdDA) neurons in the murine midbrain. Specifically, Ngn2 and Mash1 are known to have a role in the specification of neural progenitors in the ventricular zone (VZ) of the midbrain towards an mdDA neuronal cell-fate. Furthermore, other members (...) of the bHLH protein family, the E-box factors, are expressed in the developing midbrain and are thought to have a role in neuronal differentiation. Here we show that the E-box factor Tcf12 is implicated in early and late development of mdDA neurons. Tcf12 is expressed in the midbrain and in young TH-expressing mdDA neurons throughout development. Tcf12lox/lox;En1cre/+ embryos, that lose Tcf12 at ~embryonic day (E)9 throughout the En1 expression domain, have a changed spatial expression of Lmx1a and Nurr1

2017 Frontiers in molecular neuroscience

93. Amygdala–midbrain connectivity indicates a role for the mammalian parental care system in human altruism Full Text available with Trip Pro

Amygdala–midbrain connectivity indicates a role for the mammalian parental care system in human altruism Costly altruism benefitting a stranger is a rare but evolutionarily conserved phenomenon. This behaviour may be supported by limbic and midbrain circuitry that supports mammalian caregiving. In rodents, reciprocal connections between the amygdala and the midbrain periaqueductal grey (PAG) are critical for generating protective responses toward vulnerable and distressed offspring. We used

2017 Proceedings of the Royal Society B: Biological Sciences

94. Comparative Analysis of Spontaneous and Stimulus-Evoked Calcium Transients in Proliferating and Differentiating Human Midbrain-Derived Stem Cells Full Text available with Trip Pro

Comparative Analysis of Spontaneous and Stimulus-Evoked Calcium Transients in Proliferating and Differentiating Human Midbrain-Derived Stem Cells Spontaneous cytosolic calcium transients and oscillations have been reported in various tissues of nonhuman and human origin but not in human midbrain-derived stem cells. Using confocal microfluorimetry, we studied spontaneous calcium transients and calcium-regulating mechanisms in a human ventral mesencephalic stem cell line undergoing proliferation (...) the existence of a sodium-calcium antiporter and the existence of calcium influx induced by depletion of calcium stores. We conclude that the cells have developed the most important mechanisms governing cytosolic calcium homeostasis. This is the first comparative report of spontaneous calcium transients in proliferating and differentiating human midbrain-derived stem cells that provides evidence for the mechanisms that are likely to be involved. We propose that the observed spontaneous calcium transients

2017 Stem Cells International

95. Midbrain adaptation may set the stage for the perception of musical beat Full Text available with Trip Pro

Midbrain adaptation may set the stage for the perception of musical beat The ability to spontaneously feel a beat in music is a phenomenon widely believed to be unique to humans. Though beat perception involves the coordinated engagement of sensory, motor and cognitive processes in humans, the contribution of low-level auditory processing to the activation of these networks in a beat-specific manner is poorly understood. Here, we present evidence from a rodent model that midbrain preprocessing (...) of sounds may already be shaping where the beat is ultimately felt. For the tested set of musical rhythms, on-beat sounds on average evoked higher firing rates than off-beat sounds, and this difference was a defining feature of the set of beat interpretations most commonly perceived by human listeners over others. Basic firing rate adaptation provided a sufficient explanation for these results. Our findings suggest that midbrain adaptation, by encoding the temporal context of sounds, creates points

2017 Proceedings of the Royal Society B: Biological Sciences

96. Influence of envelope waveform on ITD sensitivity of neurons in the auditory midbrain Full Text available with Trip Pro

Influence of envelope waveform on ITD sensitivity of neurons in the auditory midbrain Interaural time differences (ITDs) conveyed by the modulated envelopes of high-frequency sounds can serve as a cue for localizing a sound source. Klein-Hennig et al. (J Acoust Soc Am 129: 3856, 2011) demonstrated the envelope attack (the rate at which stimulus energy in the envelope increases) and the duration of the pause (the interval between successive envelope pulses) as important factors affecting (...) sensitivity to envelope ITDs in human listeners. Modulated sounds with rapid attacks and long pauses produce the lowest ITD discrimination thresholds. The duration of the envelope's sustained component (sustain) and the rate at which stimulus energy falls at the offset of the envelope (decay) are only minor factors. We assessed the responses of 71 single neurons, recorded from the midbrains of 15 urethane-anesthetized tri-colored guinea pigs, to envelope shapes in which the four envelope components, i.e

2017 Journal of neurophysiology

97. Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line Full Text available with Trip Pro

Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line The temporal dynamic expression of Sonic Hedgehog (SHH) and signaling during early midbrain dopaminergic (mDA) neuron development is one of the key players in establishing mDA progenitor diversity. However, whether SHH signaling is also required during later developmental stages and in mature mDA neurons is less understood. We study the expression of SHH (...) receptors Ptch1 and Gas1 (growth arrest-specific 1) and of the transcription factors Gli1, Gli2 and Gli3 in mouse midbrain during embryonic development [embryonic day (E) 12.5 onwards)], in newborn and adult mice using in situ hybridization and immunohistochemistry. Moreover, we examine the expression and regulation of dopaminergic neuronal progenitor markers, midbrain dopaminergic neuronal markers and markers of the SHH signaling pathway in undifferentiated and butyric acid-treated (differentiated

2017 Cell and tissue research

98. Direct midbrain dopamine input to the suprachiasmatic nucleus accelerates circadian entrainment Full Text available with Trip Pro

Direct midbrain dopamine input to the suprachiasmatic nucleus accelerates circadian entrainment Dopamine (DA) neurotransmission controls behaviors important for survival, including voluntary movement, reward processing, and detection of salient events, such as food or mate availability. Dopaminergic tone also influences circadian physiology and behavior. Although the evolutionary significance of this input is appreciated, its precise neurophysiological architecture remains unknown. Here, we

2017 Current biology : CB

99. Wernekink Commissure Syndrome Secondary to Bilateral Caudal Paramedian Midbrain Infarction Presenting with a Unique “Heart or V” Appearance Sign: Case Report and Review of the Literature Full Text available with Trip Pro

Wernekink Commissure Syndrome Secondary to Bilateral Caudal Paramedian Midbrain Infarction Presenting with a Unique “Heart or V” Appearance Sign: Case Report and Review of the Literature Wernekink commissure syndrome secondary to caudal paramedian midbrain infarction (CPMI) is a rare midbrain syndrome involving the decussation of the superior cerebellar peduncle in the caudal paramedian midbrain tegmentum. The central characteristics are constant bilateral cerebellar dysfunction, variable (...) eye movement disorders, and rare delayed palatal myoclonus. Following is a description of the case of a 60-year-old man who presented with dizziness, slurred speech, and difficulty walking. Neurological examination revealed bilateral cerebellar dysfunction and bilateral internuclear ophthalmoplegia (bilateral INO). Serial magnetic resonance imaging (MRI) revealed a lesion in the caudal paramedian midbrain with a "heart-shaped" sign on fluid-attenuation inversion recovery images and a "V-shaped

2017 Frontiers in neurology

100. Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling Full Text available with Trip Pro

Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling A constriction in the neural tube at the junction of the midbrain and hindbrain is a conserved feature of vertebrate embryos. The constriction is a defining feature of the midbrain-hindbrain boundary (MHB), a signaling center that patterns the adjacent midbrain and rostral hindbrain and forms at the junction of two gene expression domains in the early neural plate: an anterior otx2/wnt1 positive domain

2017 Frontiers in neuroanatomy

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