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https://www.readbyqxmd.com/read/29792867/effects-of-amphetamine-exposure-during-adolescence-on-behavior-and-prelimbic-cortex-neuron-activity-in-adulthood
#1
Luke K Sherrill, Joshua M Gulley
Repeated exposure to psychostimulants during adolescence produces long-lasting changes in behavior that may be mediated by disrupted development of the mesocorticolimbic dopamine system. Here, we tested this hypothesis by assessing the effects of amphetamine (AMPH) and dopamine receptor-selective drugs on behavior and neuron activity in the prelimbic region of the medial prefrontal cortex (PFC). Adolescent male, Sprague-Dawley rats were given saline or 3 mg/kg AMPH between postnatal day (P) 27 and P45. In Experiment 1, locomotor behavior was assessed during adulthood following challenges with a dopamine D1 (SKF 82958) or D2 (quinpirole) receptor-selective agonist...
May 21, 2018: Brain Research
https://www.readbyqxmd.com/read/29791852/melanopsin-retinal-ganglion-cells-regulate-cone-photoreceptor-lamination-in-the-mouse-retina
#2
Adele R Tufford, Jessica R Onyak, Katelyn B Sondereker, Jasmine A Lucas, Aaron M Earley, Pierre Mattar, Samer Hattar, Tiffany M Schmidt, Jordan M Renna, Michel Cayouette
Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light-evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29790837/modulation-of-spinal-motor-networks-by-astrocyte-derived-adenosine-is-dependent-on-d1-like-dopamine-receptor-signalling
#3
David Acton, Matthew J Broadhead, Gareth Brian Miles
Astrocytes modulate many neuronal networks, including spinal networks responsible for the generation of locomotor behaviour. Astrocytic modulation of spinal motor circuits involves release of ATP from astrocytes, hydrolysation of ATP to adenosine, and subsequent activation of neuronal A1 adenosine receptors (A1Rs). The net effect of this pathway is a reduction in the frequency of locomotor-related activity. Recently, it was proposed that A1Rs modulate burst frequency by blocking the D1-like dopamine receptor (D1LR) signalling pathway; however, adenosine also modulates ventral horn circuits by dopamine-independent pathways...
May 23, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29790422/autologous-induced-pluripotent-stem-cell-derived-neurons-to-treat-parkinson-s-disease
#4
Jeanne F Loring
In 2012, we planned a program to develop a neuron replacement therapy for Parkinson's disease (PD) that would have the greatest promise to help the patients. PD is a movement disorder caused by the progressive, inevitable loss of a specific type of dopamine neuron in the brain. The only viable treatment to reverse the progress of the disease is to replace those neurons; we decided to make dopamine neurons that matched the patients, by differentiating induced pluripotent stem cells (iPSCs) that we generated from individuals with PD...
May 23, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29789932/the-cognitive-nuances-of-surprising-events-exposure-to-unexpected-stimuli-elicits-firing-variations-in-neurons-of-the-dorsal-ca1-hippocampus
#5
Ornella Valenti, Nace Mikus, Thomas Klausberger
The ability to recognize novel situations is among the most fascinating and vital of the brain functions. A hypothesis posits that encoding of novelty is prompted by failures in expectancy, according to computation matching incoming information with stored events. Thus, unexpected changes in context are detected within the hippocampus and transferred to downstream structures, eliciting the arousal of the dopamine system. Nevertheless, the precise locus of detection is a matter of debate. The dorsal CA1 hippocampus (dCA1) appears as an ideal candidate for operating a mismatch computation and discriminating the occurrence of diverse stimuli within the same environment...
May 22, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29789702/parallel-descending-dopaminergic-connectivity-of-a13-cells-to-the-brainstem-locomotor-centers
#6
Sandeep Sharma, Linda H Kim, Kyle A Mayr, David A Elliott, Patrick J Whelan
The mesencephalic locomotor region (MLR) is an important integrative area for the initiation and modulation of locomotion. Recently it has been realized that dopamine (DA) projections from the substantia nigra pars compacta project to the MLR. Here we explore DA projections from an area of the medial zona incerta (ZI) known for its role in motor control onto the MLR. We provide evidence that dopaminergic (DAergic) A13 neurons have connectivity to the cuneiform nucleus (CnF) and pedunculopontine tegmental nucleus (PPTg) of the MLR...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29788902/dystonia-deafness-syndrome-caused-by-actb-p-arg183trp-heterozygosity-shows-striatal-dopaminergic-dysfunction-and-response-to-pallidal-stimulation
#7
Inger Marie Skogseid, Oddveig Røsby, Ane Konglund, James P Connelly, Bård Nedregaard, Greg Eigner Jablonski, Nadja Kvernmo, Asbjørg Stray-Pedersen, Joel C Glover
BACKGROUND: Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally...
May 22, 2018: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/29786422/mechanisms-regulating-the-association-of-protein-phosphatase-1-with-spinophilin-and-neurabin
#8
Michael C Edler, Asma B Salek, Darryl S Watkins, Harjot Kaur, Cameron W Morris, Bryan K Yamamoto, Anthony J Baucum
Protein phosphorylation is a key mediator of signal transduction, allowing for dynamic regulation of substrate activity. Whereas protein kinases obtain substrate specificity by targeting specific amino acid sequences, serine/threonine phosphatase catalytic subunits are much more promiscuous in their ability to dephosphorylate substrates. To obtain substrate specificity, serine/threonine phosphatases utilize targeting proteins to regulate phosphatase subcellular localization and catalytic activity. Spinophilin and its homolog neurabin are two of the most abundant dendritic spine-localized protein phosphatase 1 (PP1) targeting proteins...
May 22, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29786160/aberrant-learning-in-parkinson-s-disease-a-neurocomputational-study-on-bradykinesia
#9
Mauro Ursino, Chiara Baston
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology...
May 22, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29786085/chronic-crh-depletion-from-gabaergic-long-range-projection-neurons-in-the-extended-amygdala-reduces-dopamine-release-and-increases-anxiety
#10
Nina Dedic, Claudia Kühne, Mira Jakovcevski, Jakob Hartmann, Andreas J Genewsky, Karina S Gomes, Elmira Anderzhanova, Max L Pöhlmann, Simon Chang, Adam Kolarz, Annette M Vogl, Julien Dine, Michael W Metzger, Bianca Schmid, Rafael C Almada, Kerry J Ressler, Carsten T Wotjak, Valery Grinevich, Alon Chen, Mathias V Schmidt, Wolfgang Wurst, Damian Refojo, Jan M Deussing
The interplay between corticotropin-releasing hormone (CRH) and the dopaminergic system has predominantly been studied in addiction and reward, while CRH-dopamine interactions in anxiety are scarcely understood. We describe a new population of CRH-expressing, GABAergic, long-range-projecting neurons in the extended amygdala that innervate the ventral tegmental area and alter anxiety following chronic CRH depletion. These neurons are part of a distinct CRH circuit that acts anxiolytically by positively modulating dopamine release...
May 21, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29786072/mptp-driven-nlrp3-inflammasome-activation-in-microglia-plays-a-central-role-in-dopaminergic-neurodegeneration
#11
Eunju Lee, Inhwa Hwang, Sangjun Park, Sujeong Hong, Boreum Hwang, Yoeseph Cho, Junghyun Son, Je-Wook Yu
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the reduction of dopamine levels in the striatum. Although details of the molecular mechanisms underlying dopaminergic neuronal death in PD remain unclear, neuroinflammation is also considered a potent mediator in the pathogenesis and progression of PD. In the present study, we present evidences that microglial NLRP3 inflammasome activation is critical for dopaminergic neuronal loss and the subsequent motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785351/genetic-inactivation-of-alpha-synuclein-affects-embryonic-development-of-dopaminergic-neurons-of-the-substantia-nigra-but-not-the-ventral-tegmental-area-in-mouse-brain
#12
Tatiana V Tarasova, Olga A Lytkina, Valeria V Goloborshcheva, Larisa N Skuratovskaya, Alexandr I Antohin, Ruslan K Ovchinnikov, Michail S Kukharsky
Lesion of the dopaminergic neurons of the nigrostriatal system is a key feature of Parkinson's disease (PD). Alpha-synuclein is a protein that is a major component of Lewy bodies, histopathological hallmarks of PD, and is involved in regulation of dopamine (DA) neurotransmission. Previous studies of knockout mice have shown that inactivation of alpha-synuclein gene can lead to the reduction in number of DA neurons in the substantia nigra (SN). DA neurons of the SN are known to be the most affected in PD patients whereas DA neurons of neighboring ventral tegmental area (VTA) are much less susceptible to degeneration...
2018: PeerJ
https://www.readbyqxmd.com/read/29783994/large-scale-transcriptomic-analysis-reveals-that-pridopidine-reverses-aberrant-gene-expression-and-activates-neuroprotective-pathways-in-the-yac128-hd-mouse
#13
Rebecca Kusko, Jennifer Dreymann, Jermaine Ross, Yoonjeong Cha, Renan Escalante-Chong, Marta Garcia-Miralles, Liang Juin Tan, Michael E Burczynski, Ben Zeskind, Daphna Laifenfeld, Mahmoud Pouladi, Michal Geva, Iris Grossman, Michael R Hayden
BACKGROUND: Huntington Disease (HD) is an incurable autosomal dominant neurodegenerative disorder driven by an expansion repeat giving rise to the mutant huntingtin protein (mHtt), which is known to disrupt a multitude of transcriptional pathways. Pridopidine, a small molecule in development for treatment of HD, has been shown to improve motor symptoms in HD patients. In HD animal models, pridopidine exerts neuroprotective effects and improves behavioral and motor functions. Pridopidine binds primarily to the sigma-1 receptor, (IC50 ~ 100 nM), which mediates its neuroprotective properties, such as rescue of spine density and aberrant calcium signaling in HD neuronal cultures...
May 21, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29783725/polyphenols-in-parkinson-s-disease-a-systematic-review-of-in-vivo-studies
#14
REVIEW
Małgorzata Kujawska, Jadwiga Jodynis-Liebert
Parkinson's disease (PD) is the second most common neurodegenerative disorder. However, therapeutic options treating only its symptoms are very disappointing. Therefore there is an ongoing search for compounds capable of tackling the multi-dimensional features of PD. Recently natural polyphenols have gained great interest as potential therapeutic agents. Herein, we have attempted to summarize results obtained in different animal models demonstrating their neuroprotective effects. The in vivo findings presented below are supported by human subject data and reports regarding the ability of polyphenols to cross the blood-brain barrier...
May 19, 2018: Nutrients
https://www.readbyqxmd.com/read/29782942/effects-of-light-and-dark-phase-testing-on-the-investigation-of-behavioural-paradigms-in-mice-relevance-for-behavioural-neuroscience
#15
Juliet Richetto, Marcello Polesel, Ulrike Weber-Stadlbauer
Different timing and light phases are critical factors in behavioural neuroscience, which can greatly affect the experimental outcomes of the performed tests. Despite the fact that time of testing is one of the most common factors that varies across behavioural laboratories, knowledge about the consequences of testing time on behavioural readouts is limited. Thus, in this study we systematically assessed the effect of this factor on the readout of a variety of elementary and recurrent behavioural paradigms in C57Bl/6 mice...
May 18, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29782882/prolonged-increase-in-ser31-tyrosine-hydroxylase-phosphorylation-in-substantia-nigra-following-cessation-of-chronic-methamphetamine
#16
Michael F Salvatore, Vicki A Nejtek, Habibeh Khoshbouei
Methamphetamine (MA) exposure may increase the risk of motor or cognitive impairments similar to Parkinson's disease (PD) by middle age. Although damage to nigrostriatal or mesoaccumbens dopamine (DA) neurons may occur during or early after MA exposure, overt PD-like symptoms at a younger age may not manifest due to compensatory mechanisms to maintain DA neurotransmission. One possible compensatory mechanism is increased tyrosine hydroxylase (TH) phosphorylation. In the rodent PD 6-OHDA model, nigrostriatal lesion decreases TH protein in both striatum and substantia nigra (SN)...
May 18, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29781560/conditioned-reward-of-opioids-but-not-psychostimulants-is-impaired-in-gaba-a-receptor-%C3%AE-subunit-knockout-mice
#17
Milo S Siivonen, Elena de Miguel, Juho Aaltio, Aino K Manner, Mikko Vahermo, Jari Yli-Kauhaluoma, Anni-Maija Linden, Teemu Aitta-Aho, Esa R Korpi
Extrasynaptic δ subunit-containing γ-aminobutyric acid type A receptors (δ-GABAA Rs) are emerging as targets for a number of neuropsychopharmacological drugs, including the direct GABA-site agonist gaboxadol and neuroactive steroids. Among other regions, these δ-GABAA Rs are functionally expressed in the ventral tegmental area (VTA), the cell body region of mesocorticolimbic dopamine (DA) system important for motivated behaviors, and in the target region, the nucleus accumbens. Gaboxadol and neurosteroids induce VTA DA neuron plasticity ex vivo, by inhibiting the VTA GABA neurons, and aversive place conditioning, which are absent in the δ-GABAA R knockout mice (δ-KO)...
May 21, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29781098/pet-imaging-of-the-influence-of-physiological-and-pathological-%C3%AE-synuclein-on-dopaminergic-and-serotonergic-neurotransmission-in-mouse-models
#18
Elise Levigoureux, Caroline Bouillot, Thierry Baron, Luc Zimmer, Sophie Lancelot
AIMS: Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of neurodegenerative synucleinopathies. This in vivo study explored glucose metabolism and dopaminergic and serotoninergic neurotransmission in KO α-syn, wild-type mice and an accelerated murine model of synucleinopathy (M83). METHODS: MicroPET acquisitions were performed in all animals aged 5-6 months using five radiotracers exploring brain glucose metabolism ([18 F]FDG), dopamine neurotransmission ([11 C]raclopride, [11 C]PE2I) and serotonin neurotransmission ([18 F]MPPF, [11 C]DASB)...
May 20, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29780881/nucleus-accumbens-microcircuit-underlying-d2-msn-driven-increase-in-motivation
#19
Carina Soares-Cunha, Bárbara Coimbra, Ana Verónica Domingues, Nivaldo Vasconcelos, Nuno Sousa, Ana João Rodrigues
The nucleus accumbens (NAc) plays a central role in reinforcement and motivation. Around 95% of the NAc neurons are medium spiny neurons (MSNs), divided into those expressing dopamine receptor D1 (D1R) or dopamine receptor D2 (D2R). Optogenetic activation of D2-MSNs increased motivation, whereas inhibition of these neurons produced the opposite effect. Yet, it is still unclear how activation of D2-MSNs affects other local neurons/interneurons or input terminals and how this contributes for motivation enhancement...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29779874/a-gabaergic-feedback-shapes-dopaminergic-input-on-the-drosophila-mushroom-body-to-promote-appetitive-long-term-memory
#20
Alice Pavlowsky, Johann Schor, Pierre-Yves Plaçais, Thomas Preat
Memory consolidation is a crucial step for long-term memory (LTM) storage. However, we still lack a clear picture of how memory consolidation is regulated at the neuronal circuit level. Here, we took advantage of the well-described anatomy of the Drosophila olfactory memory center, the mushroom body (MB), to address this question in the context of appetitive LTM. The MB lobes, which are made by the fascicled axons of the MB intrinsic neurons, are organized into discrete anatomical modules, each covered by the terminals of a defined type of dopaminergic neuron (DAN) and the dendrites of a corresponding type of MB output neuron (MBON)...
May 9, 2018: Current Biology: CB
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