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https://www.readbyqxmd.com/read/28097219/key-role-of-the-dopamine-d4-receptor-in-the-modulation-of-corticostriatal-glutamatergic-neurotransmission
#1
Jordi Bonaventura, César Quiroz, Ning-Sheng Cai, Marcelo Rubinstein, Gianluigi Tanda, Sergi Ferré
Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D4 receptor with the long intracellular domain of a human DRD4 polymorphic variant associated with attention deficit hyperactivity disorder (ADHD)...
January 2017: Science Advances
https://www.readbyqxmd.com/read/28069435/astrocytes-and-presynaptic-plasticity-in-the-striatum-evidence-and-unanswered-questions
#2
Anton Dvorzhak, Igor Melnick, Rosemarie Grantyn
One of the main functions of astrocytes is to ensure glutamate homeostasis by glutamate uptake and glutamine synthesis. However, during the past ten years it has become clear that astrocytes may also induce changes in synaptic glutamate release when respective pathways must cope with the consequences of brain damage or other alterations in their functional requirements. The loss of glutamatergic synapses in Parkinson's and Huntington's disease is likely to associate with a continuous redistribution of presynaptic activity within the pool of surviving synapses, and astrocytes may have a role in the maintenance of independent control at individual glutamate release sites...
January 6, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28067279/impaired-novelty-acquisition-and-synaptic-plasticity-in-congenital-hyperammonemia-caused-by-hepatic-glutamine-synthetase-deficiency
#3
Aisa N Chepkova, Olga A Sergeeva, Boris Görg, Helmut L Haas, Nikolaj Klöcker, Dieter Häussinger
Genetic defects in ammonia metabolism can produce irreversible damage of the developing CNS causing an impairment of cognitive and motor functions. We investigated alterations in behavior, synaptic plasticity and gene expression in the hippocampus and dorsal striatum of transgenic mice with systemic hyperammonemia resulting from conditional knockout of hepatic glutamine synthetase (LGS-ko). These mice showed reduced exploratory activity and delayed habituation to a novel environment. Field potential recordings from LGS-ko brain slices revealed significantly reduced magnitude of electrically-induced long-term potentiation (LTP) in both CA3-CA1 hippocampal and corticostriatal synaptic transmission...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28018188/cholinergic-interneurons-amplify-corticostriatal-synaptic-responses-in-the-q175-model-of-huntington-s-disease
#4
Asami Tanimura, Sean Austin O Lim, Jose de Jesus Aceves Buendia, Joshua A Goldberg, D James Surmeier
Huntington's disease (HD) is a neurodegenerative disorder characterized by deficits in movement control that are widely viewed as stemming from pathophysiological changes in the striatum. Giant, aspiny cholinergic interneurons (ChIs) are key elements in the striatal circuitry controlling movement, but whether their physiological properties are intact in the HD brain is unclear. To address this issue, the synaptic properties of ChIs were examined using optogenetic approaches in the Q175 mouse model of HD. In ex vivo brain slices, synaptic facilitation at thalamostriatal synapses onto ChIs was reduced in Q175 mice...
2016: Frontiers in Systems Neuroscience
https://www.readbyqxmd.com/read/28007645/parkinson-s-disease-associated-gpr37-receptor-regulates-cocaine-mediated-synaptic-depression-in-corticostriatal-synapses
#5
Daniel Rial, Xavier Morató, Joana I Real, Francisco Q Gonçalves, Igor Stagljar, Frederico C Pereira, Víctor Fernández-Dueñas, Rodrigo A Cunha, Francisco Ciruela
GPR37 is an orphan G protein-coupled receptor highly expressed in the brain. The precise function of GPR37 is still unknown, but a number of evidences indicate it modulates the dopaminergic system. Here, we aimed to determine the role of GPR37 on the control of cocaine-mediated electrophysiological effects (synaptic transmission and short-term plasticity) in corticostriatal synapses. Accordingly, we evaluated basal synaptic transmission and paired-pulse stimulation (PPS) in wild-type and GPR37KO mice slices...
December 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27983564/dysregulation-of-corticostriatal-connectivity-in-huntington-s-disease-a%C3%A2-role-for-dopamine-modulation
#6
Claudia Rangel-Barajas, George V Rebec
Aberrant communication between striatum, the main information processing unit of the basal ganglia, and cerebral cortex plays a critical role in the emergence of Huntington's disease (HD), a fatal monogenetic condition that typically strikes in the prime of life. Although both striatum and cortex undergo substantial cell loss over the course of HD, corticostriatal circuits become dysfunctional long before neurons die. Understanding the dysfunction is key to developing effective strategies for treating a progressively worsening triad of motor, cognitive, and psychiatric symptoms...
December 15, 2016: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/27974817/rats-overexpressing-the-dopamine-transporter-display-behavioral-and-neurobiological-abnormalities-with-relevance-to-repetitive-disorders
#7
Ravit Hadar, Henriette Edemann-Callesen, Claudia Reinel, Franziska Wieske, Mareike Voget, Elena Popova, Reinhard Sohr, Yosef Avchalumov, Josef Priller, Christoph van Riesen, Imke Puls, Michael Bader, Christine Winter
The dopamine transporter (DAT) plays a pivotal role in maintaining optimal dopamine signaling. DAT-overactivity has been linked to various neuropsychiatric disorders yet so far the direct pathological consequences of it has not been fully assessed. We here generated a transgenic rat model that via pronuclear microinjection overexpresses the DAT gene. Our results demonstrate that DAT-overexpression induces multiple neurobiological effects that exceeded the expected alterations in the corticostriatal dopamine system...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27932974/patterns-of-longitudinal-neural-activity-linked-to-different-cognitive-profiles-in-parkinson-s-disease
#8
Atsuko Nagano-Saito, Mohamed S Al-Azzawi, Alexandru Hanganu, Clotilde Degroot, Béatriz Mejia-Constain, Christophe Bedetti, Anne-Louise Lafontaine, Valérie Soland, Sylvain Chouinard, Oury Monchi
Mild cognitive impairment in Parkinson's disease (PD) has been linked with functional brain changes. Previously, using functional magnetic resonance imaging (fMRI), we reported reduced cortico-striatal activity in patients with PD who also had mild cognitive impairment (MCI) vs. those who did not (non-MCI). We followed up these patients to investigate the longitudinal effect on the neural activity. Twenty-four non-demented patients with Parkinson's disease (non-MCI: 12, MCI: 12) were included in the study. Each participant underwent two fMRIs while performing the Wisconsin Card Sorting Task 20 months apart...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27916455/phosphodiesterase-10a-inhibition-improves-cortico-basal-ganglia-function-in-huntington-s-disease-models
#9
Vahri Beaumont, Sheng Zhong, Hai Lin, WenJin Xu, Amyaouch Bradaia, Esther Steidl, Melanie Gleyzes, Kristian Wadel, Bruno Buisson, Fernando E Padovan-Neto, Shreaya Chakroborty, Karen M Ward, John F Harms, Jose Beltran, Mei Kwan, Afshin Ghavami, Jenny Häggkvist, Miklós Tóth, Christer Halldin, Andrea Varrone, Christoph Schaab, J Nikolaj Dybowski, Sarah Elschenbroich, Kimmo Lehtimäki, Taneli Heikkinen, Larry Park, James Rosinski, Ladislav Mrzljak, Daniel Lavery, Anthony R West, Christopher J Schmidt, Margaret M Zaleska, Ignacio Munoz-Sanjuan
Huntington's disease (HD) symptoms are driven to a large extent by dysfunction of the basal ganglia circuitry. HD patients exhibit reduced striatal phoshodiesterase 10 (PDE10) levels. Using HD mouse models that exhibit reduced PDE10, we demonstrate the benefit of pharmacologic PDE10 inhibition to acutely correct basal ganglia circuitry deficits. PDE10 inhibition restored corticostriatal input and boosted cortically driven indirect pathway activity. Cyclic nucleotide signaling is impaired in HD models, and PDE10 loss may represent a homeostatic adaptation to maintain signaling...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/27907134/reward-contingencies-improve-goal-directed-behavior-by-enhancing-posterior-brain-attentional-regions-and-increasing-corticostriatal-connectivity-in-cocaine-addicts
#10
Patricia Rosell-Negre, Juan-Carlos Bustamante, Paola Fuentes-Claramonte, Víctor Costumero, Juan-José Llopis-Llacer, Alfonso Barrós-Loscertales
The dopaminergic system provides the basis for the interaction between motivation and cognition. It is triggered by the possibility of obtaining rewards to initiate the neurobehavioral adaptations necessary to achieve them by directing the information from motivational circuits to cognitive and action circuits. In drug addiction, the altered dopamine (DA) modulation of the meso-cortico-limbic reward circuitry, such as the prefrontal cortex (PFC), underlies the disproportionate motivational value of drug use at the expense of other non-drug reinforcers and the user's loss of control over his/her drug intake...
2016: PloS One
https://www.readbyqxmd.com/read/27877117/general-habit-propensity-relates-to-the-sensation-seeking-subdomain-of-impulsivity-but-not-obesity
#11
Anja Dietrich, Sanne de Wit, Annette Horstmann
According to dual-system theory, instrumental learning and performance depend on the balance between goal-directed and habitual action control. Overreliance on habits has been argued to characterize clinical conditions such as drug addiction or obsessive-compulsive disorder as well as obesity and excessive impulsivity. A tendency toward habitual action control in obesity has already been indicated in the food domain. However, impairments might not be restricted to eating behavior. This has been suggested by domain-general obesity-associated disturbances in executive function as well as alterations in corticostriatal circuits underlying the goal-directed and habitual systems...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27859903/corticostriatal-connectivity-fingerprints-probability-maps-based-on-resting-state-functional-connectivity
#12
Ellen Jaspers, Joshua H Balsters, Pegah Kassraian Fard, Dante Mantini, Nicole Wenderoth
Over the last decade, structure-function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level...
November 12, 2016: Human Brain Mapping
https://www.readbyqxmd.com/read/27859864/l-dopa-induced-dyskinesia-and-neuroinflammation-do-microglia-and-astrocytes-play-a-role
#13
REVIEW
Anna R Carta, Giovanna Mulas, Mariza Bortolanza, Terence Duarte, Elisabetta Pillai, Gilberto Fisone, Rita Raisman Vozari, Elaine Del-Bel
In Parkinson's disease (PD), l-DOPA therapy leads to the emergence of motor complications including l-DOPA-induced dyskinesia (LID). LID relies on a sequence of pre- and postsynaptic neuronal events, leading to abnormal corticostriatal neurotransmission and maladaptive changes in striatal projection neurons. In recent years, additional non-neuronal mechanisms have been proposed to contribute to LID. Among these mechanisms, considerable attention has been focused on l-DOPA-induced inflammatory responses. Microglia and astrocytes are the main actors in neuroinflammatory responses, and their double role at the interface between immune and neurophysiological responses is starting to be elucidated...
January 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27826070/research-domain-criteria-versus-dsm-v-how-does-this-debate-affect-attempts-to-model-corticostriatal-dysfunction-in-animals
#14
REVIEW
Jared W Young, Catharine A Winstanley, Anne Marie Brady, Frank Scott Hall
For decades, the nosology of mental illness has been based largely upon the descriptions in the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM). A recent challenge to the DSM approach to psychiatric nosology from the National Institute on Mental Health (USA) defines Research Domain Criteria (RDoC) as an alternative. For RDoC, psychiatric illnesses are not defined as discrete categories, but instead as specific behavioral dysfunctions irrespective of DSM diagnostic categories...
November 5, 2016: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/27818324/the-sigma-1-receptor-mediates-the-beneficial-effects-of-pridopidine-in-a-mouse-model-of-huntington-disease
#15
Daniel Ryskamp, Jun Wu, Michal Geva, Rebecca Kusko, Iris Grossman, Michael Hayden, Ilya Bezprozvanny
The tri-nucleotide repeat expansion underlying Huntington disease (HD) results in corticostriatal synaptic dysfunction and subsequent neurodegeneration of striatal medium spiny neurons (MSNs). HD is a devastating autosomal dominant disease with no disease-modifying treatments. Pridopidine, a postulated "dopamine stabilizer", has been shown to improve motor symptoms in clinical trials of HD. However, the target(s) and mechanism of action of pridopidine remain to be fully elucidated. As binding studies identified sigma-1 receptor (S1R) as a high-affinity receptor for pridopidine, we evaluated the relevance of S1R as a therapeutic target of pridopidine in HD...
January 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/27816502/dysregulated-corticostriatal-activity-in-open-field-behavior-and-the-head-twitch-response-induced-by-the-hallucinogen-2-5-dimethoxy-4-iodoamphetamine
#16
Claudia Rangel-Barajas, Ana María Estrada-Sánchez, Scott J Barton, Robert R Luedtke, George V Rebec
The substituted amphetamine, 2,5-dimethoxy-4-iodoamphetamine (DOI), is a hallucinogen that has been used to model a variety of psychiatric conditions. Here, we studied the effect of DOI on neural activity recorded simultaneously in the primary motor cortex (M1) and dorsal striatum of freely behaving FvB/N mice. DOI significantly decreased the firing rate of individually isolated neurons in M1 and dorsal striatum relative to pre-drug baseline. It also induced a bursting pattern of activity by increasing both the number of spikes within a burst and burst duration...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27797829/genome-wide-transcriptional-profiling-and-structural-magnetic-resonance-imaging-in-the-maternal-immune-activation-model-of-neurodevelopmental-disorders
#17
Juliet Richetto, Robert Chesters, Annamaria Cattaneo, Marie A Labouesse, Ana Maria Carrillo Gutierrez, Tobias C Wood, Alessia Luoni, Urs Meyer, Anthony Vernon, Marco A Riva
Prenatal exposure to maternal infection increases the risk of neurodevelopmental disorders, including schizophrenia and autism. The molecular processes underlying this pathological association, however, are only partially understood. Here, we combined unbiased genome-wide transcriptional profiling with follow-up epigenetic analyses and structural magnetic resonance imaging to explore convergent molecular and neuromorphological alterations in corticostriatal areas of adult offspring exposed to prenatal immune activation...
October 23, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27771973/dopaminergic-enhancement-of-striatal-response-to-reward-in-major-depression
#18
Roee Admon, Roselinde H Kaiser, Daniel G Dillon, Miranda Beltzer, Franziska Goer, David P Olson, Gordana Vitaliano, Diego A Pizzagalli
OBJECTIVE: Major depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals. METHOD: In a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D2/D3 receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade...
October 24, 2016: American Journal of Psychiatry
https://www.readbyqxmd.com/read/27766766/region-specific-activation-of-the-akt-and-mtorc1-pathway-in-response-to-excessive-alcohol-intake-in-rodents
#19
Sophie Laguesse, Nadege Morisot, Khanhky Phamluong, Dorit Ron
We previously reported that the kinase AKT is activated in the nucleus accumbens (NAc) of rodents in response to excessive consumption of alcohol. One of the important downstream targets of AKT is the mammalian Target Of Rapamycin in Complex 1 (mTORC1), which was also activated by alcohol intake. mTORC1 controls dendritic protein translation, and we showed that the mTORC1-dependent translational machinery is activated in the NAc in response to alcohol intake. Importantly, systemic or intra-NAc inhibition of the AKT/mTORC1 pathway attenuated alcohol-drinking behaviors...
October 20, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27751235/control-of-the-structural-landscape-and-neuronal-proteotoxicity-of-mutant-huntingtin-by-domains-flanking-the-polyq-tract
#20
Koning Shen, Barbara Calamini, Jonathan A Fauerbach, Boxue Ma, Sarah H Shahmoradian, Ivana L Serrano Lachapel, Wah Chiu, Donald C Lo, Judith Frydman
Many neurodegenerative diseases are linked to amyloid aggregation. In Huntington's disease (HD), neurotoxicity correlates with an increased aggregation propensity of a polyglutamine (polyQ) expansion in exon 1 of mutant huntingtin protein (mHtt). Here we establish how the domains flanking the polyQ tract shape the mHtt conformational landscape in vitro and in neurons. In vitro, the flanking domains have opposing effects on the conformation and stabilities of oligomers and amyloid fibrils. The N-terminal N17 promotes amyloid fibril formation, while the C-terminal Proline Rich Domain destabilizes fibrils and enhances oligomer formation...
October 18, 2016: ELife
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