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141. Amphetamine and Methamphetamine Increase NMDAR-GluN2B Synaptic Currents in Midbrain Dopamine Neurons. Full Text available with Trip Pro

Amphetamine and Methamphetamine Increase NMDAR-GluN2B Synaptic Currents in Midbrain Dopamine Neurons. The psychostimulants amphetamine (AMPH) and methamphetamine (MA) are widely abused illicit drugs. Here we show that both psychostimulants acutely increase NMDA receptor (NMDAR)-mediated synaptic currents and decrease AMPA receptor (AMPAR)/NMDAR ratios in midbrain dopamine neurons. The potentiation depends on the transport of AMPH into the cell by the dopamine transporter. NMDAR-GluN2B receptor (...) , indicate that potentiated NMDARs reside on the plasma membrane and are not inserted de novo. In behavioral studies, GluN2B inhibitors reduce MA-mediated locomotor activity, without affecting basal activity. These results reveal an important interaction between dopamine and glutamatergic signaling in midbrain dopamine neurons in response to acute administration of psychostimulants.

2016 Neuropsychopharmacology

142. Chemogenetic Activation of Midbrain Dopamine Neurons Affects Attention, but not Impulsivity, in the Five-Choice Serial Reaction Time-Task in Rats. Full Text available with Trip Pro

Chemogenetic Activation of Midbrain Dopamine Neurons Affects Attention, but not Impulsivity, in the Five-Choice Serial Reaction Time-Task in Rats. Attentional impairments and exaggerated impulsivity are key features of psychiatric disorders, such as attention-deficit/hyperactivity disorder, schizophrenia, and addiction. These deficits in attentional performance and impulsive behaviors have been associated with aberrant dopamine (DA) signaling, but it remains unknown whether these deficits (...) result from enhanced DA neuronal activity in the midbrain. Here, we took a novel approach by testing the impact of chemogenetically activating DA neurons in the ventral tegmental area (VTA) or substantia nigra pars compacta (SNc) on attention and impulsivity in the five-choice serial reaction time task (5-CSRTT) in rats. We found that activation of DA neurons in both the VTA and SNc impaired attention by increasing trial omissions. In addition, SNc DA neuron activation decreased attentional accuracy

2016 Neuropsychopharmacology

143. MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression. Full Text available with Trip Pro

MicroRNA-326 acts as a molecular switch in the regulation of midbrain urocortin 1 expression. Altered levels of urocortin 1 (Ucn1) in the centrally projecting Edinger-Westphal nucleus (EWcp) of depressed suicide attempters or completers mediate the brain's response to stress, while the mechanism regulating Ucn1 expression is unknown. We tested the hypothesis that microRNAs (miRNAs), which are vital fine-tuners of gene expression during the brain's response to stress, have the capacity (...) by this miRNA in cultured midbrain neurons.We found reduced miR-326 levels concomitant with elevated Ucn1 levels in the EWcp of depressed suicide completers as well as in the EWcp of CVMS rats. In CVMS rats fully recovered from stress, both serum and EWcp miR-326 levels rebounded to nonstressed levels. While downregulation of miR-326 levels in primary midbrain neurons enhanced Ucn1 expression levels, miR-326 overexpression selectively reduced the levels of this neuropeptide.This study lacked experiments

2016 Journal of Psychiatry & Neuroscience

144. Hypocretin-1 levels in the cerebrospinal fluid of patients with Percheron artery infarction with or without midbrain involvement: A case series. Full Text available with Trip Pro

Hypocretin-1 levels in the cerebrospinal fluid of patients with Percheron artery infarction with or without midbrain involvement: A case series. Bilateral paramedian thalamic infarctions (BPTIs) due to artery of Percheron occlusion are known to cause hypersomnia. However, the role of hypocretin-1, a wake-promoting peptide that is located at the lateral hypothalamus, in hypersomnia in these patients remains unclear.To clarify the role of hypocretin-1 in hypersomnia in patients with BPTIs (...) , hypocretin-1 levels in the cerebrospinal fluid (CSF) were measured in 6 patients with BPTIs: 2 with rostral midbrain involvement (BPT+RMI) and 4 without midbrain involvement (BPT-MI).CSF hypocretin-1 levels were decreased in 2 patients with BPT+RMI and were within normal ranges in 4 patients with BPT-MI. Hypersomnia was noted in all the patients. In one BPT+RMI patient, hypersomnia was improved within 2 weeks and decreased CSF hypocretin-1 levels were reversed (acute phase (on day 9), 109.2 pg/mL

2016 Medicine

145. Sex Differences in Midbrain Dopamine D2-Type Receptor Availability and Association with Nicotine Dependence. Full Text available with Trip Pro

Sex Differences in Midbrain Dopamine D2-Type Receptor Availability and Association with Nicotine Dependence. Women differ from men in smoking-related behaviors, among them a greater difficulty in quitting smoking. Unlike female smokers, male smokers have lower striatal dopamine D2-type receptor availability (binding potential, BPND) than nonsmokers and exhibit greater smoking-induced striatal dopamine release. Because dopamine D2-type autoreceptors in the midbrain influence striatal dopamine (...) release, a function that has been linked to addiction, we tested for sex differences in midbrain dopamine D2-type receptor BPND and in relationships between midbrain BPND, nicotine dependence and striatal dopamine D2-type receptor BPND. Positron emission tomography was used with [18F]fallypride to measure BPND in a midbrain region, encompassing the substantia nigra and ventral tegmental area, in 18 daily smokers (7 women, 11 men) and 19 nonsmokers (10 women, 9 men). A significant sex-by-group

2016 Neuropsychopharmacology

146. Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward. Full Text available with Trip Pro

Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward. The central melanocortin (MC) system mediates its effects on food intake via MC3 (MC3R) and MC4 receptors (MC4R). Although the role of MC4R in meal size determination, satiation, food preference, and motivation is well established, the involvement of MC3R in the modulation of food intake has been less explored. Here, we investigated the role of MC3R on the incentive motivation for food

2016 Neuropsychopharmacology

147. Ldb1 Is Essential for the Development of Isthmic Organizer and Midbrain Dopaminergic Neurons Full Text available with Trip Pro

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

2016 Stem cells and development

148. Convergence‐Retraction Nystagmus Associated with Dorsal Midbrain Lesions in Three Dogs Full Text available with Trip Pro

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

2016 Journal of Veterinary Internal Medicine

149. SLC35D3 increases autophagic activity in midbrain dopaminergic neurons by enhancing BECN1-ATG14-PIK3C3 complex formation Full Text available with Trip Pro

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

2016 Autophagy

150. D-serine in the midbrain periaqueductal gray contributes to morphine tolerance in rats Full Text available with Trip Pro

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

2016 Molecular pain

151. Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters Full Text available with Trip Pro

Physical Interactions and Functional Relationships of Neuroligin 2 and Midbrain Serotonin Transporters The neurotransmitter serotonin [5-hydroxytryptamine (5-HT)] modulates many key brain functions including those subserving sensation, emotion, reward, and cognition. Efficient clearance of 5-HT after release is achieved by the antidepressant-sensitive 5-HT transporter (SERT, SLC6A4). To identify novel SERT regulators, we pursued a proteomic analysis of mouse midbrain SERT complexes, evaluating (...) findings in the context of prior studies that established a SERT-linked transcriptome. Remarkably, both efforts converged on a relationship of SERT with the synaptic adhesion protein neuroligin 2 (NLGN2), a post-synaptic partner for presynaptic neurexins, and a protein well-known to organize inhibitory GABAergic synapses. Western blots of midbrain reciprocal immunoprecipitations confirmed SERT/NLGN2 associations, and also extended to other NLGN2 associated proteins [e.g., α-neurexin (NRXN), gephyrin

2016 Frontiers in synaptic neuroscience

152. Speech Coding in the Midbrain: Effects of Sensorineural Hearing Loss Full Text available with Trip Pro

Speech Coding in the Midbrain: Effects of Sensorineural Hearing Loss In response to voiced speech sounds, auditory-nerve (AN) fibres phase-lock to harmonics near best frequency (BF) and to the fundamental frequency (F0) of voiced sounds. Due to nonlinearities in the healthy ear, phase-locking in each frequency channel is dominated either by a single harmonic, for channels tuned near formants, or by F0, for channels between formants. The alternating dominance of these factors sets up a robust (...) pattern of F0-synchronized rate across best frequency (BF). This profile of a temporally coded measure is transformed into a mean rate profile in the midbrain (inferior colliculus, IC), where neurons are sensitive to low-frequency fluctuations. In the impaired ear, the F0-synchronized rate profile is affected by several factors: Reduced synchrony capture decreases the dominance of a single harmonic near BF on the response. Elevated thresholds also reduce the effect of rate saturation, resulting

2016 Advances in experimental medicine and biology

153. 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

154. 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

155. Adaptive Prediction Error Coding in the Human Midbrain and Striatum Facilitates Behavioral Adaptation and Learning Efficiency Full Text available with Trip Pro

Adaptive Prediction Error Coding in the Human Midbrain and Striatum Facilitates Behavioral Adaptation and Learning Efficiency Effective error-driven learning benefits from scaling of prediction errors to reward variability. Such behavioral adaptation may be facilitated by neurons coding prediction errors relative to the standard deviation (SD) of reward distributions. To investigate this hypothesis, we required participants to predict the magnitude of upcoming reward drawn from distributions

2016 Neuron

156. Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors Full Text available with Trip Pro

Dopamine Receptor Antagonists Enhance Proliferation and Neurogenesis of Midbrain Lmx1a-expressing Progenitors Degeneration of dopamine neurons in the midbrain causes symptoms of the movement disorder, Parkinson disease. Dopamine neurons are generated from proliferating progenitor cells localized in the embryonic ventral midbrain. However, it remains unclear for how long cells with dopamine progenitor character are retained and if there is any potential for reactivation of such cells after (...) cessation of normal dopamine neurogenesis. We show here that cells expressing Lmx1a and other progenitor markers remain in the midbrain aqueductal zone beyond the major dopamine neurogenic period. These cells express dopamine receptors, are located in regions heavily innervated by midbrain dopamine fibres and their proliferation can be stimulated by antagonizing dopamine receptors, ultimately leading to increased neurogenesis in vivo. Furthermore, treatment with dopamine receptor antagonists enhances

2016 Scientific reports

157. 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

158. 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

159. 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

160. Development and Dynamic Regulation of Mitochondrial Network in Human Midbrain Dopaminergic Neurons Differentiated from iPSCs Full Text available with Trip Pro

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

2016 Stem cell reports

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