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https://www.readbyqxmd.com/read/28798678/striatal-neuropeptides-enhance-selection-and-rejection-of-sequential-actions
#1
David Buxton, Enrico Bracci, Paul G Overton, Kevin Gurney
The striatum is the primary input nucleus for the basal ganglia, and receives glutamatergic afferents from the cortex. Under the hypothesis that basal ganglia perform action selection, these cortical afferents encode potential "action requests." Previous studies have suggested the striatum may utilize a mutually inhibitory network of medium spiny neurons (MSNs) to filter these requests so that only those of high salience are selected. However, the mechanisms enabling the striatum to perform clean, rapid switching between distinct actions that form part of a learned action sequence are still poorly understood...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28790376/global-and-local-excitation-and-inhibition-shape-the-dynamics-of-the-cortico-striatal-thalamo-cortical-pathway
#2
Anca Rădulescu, Joanna Herron, Caitlin Kennedy, Annalisa Scimemi
The cortico-striatal-thalamo-cortical (CSTC) pathway is a brain circuit that controls movement execution, habit formation and reward. Hyperactivity in the CSTC pathway is involved in obsessive compulsive disorder (OCD), a neuropsychiatric disorder characterized by the execution of repetitive involuntary movements. The striatum shapes the activity of the CSTC pathway through the coordinated activation of two classes of medium spiny neurons (MSNs) expressing D1 or D2 dopamine receptors. The exact mechanisms by which balanced excitation/inhibition (E/I) of these cells controls the network dynamics of the CSTC pathway remain unclear...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782235/detection-of-phasic-dopamine-by-d1-and-d2-striatal-medium-spiny-neurons
#3
Cedric Yapo, Anu G Nair, Lorna Clement, Liliana R Castro, Jeanette Hellgren Kotaleski, Pierre Vincent
The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of dopamine effect on intracellular signalling remains poorly understood. We used genetically-encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation level, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively...
August 7, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28780133/altered-glua1-gria1-function-and-accumbal-synaptic-plasticity-in-the-clock%C3%AE-19-model-of-bipolar-mania
#4
Puja K Parekh, Darius Becker-Krail, Poornima Sundaravelu, Shinsuke Ishigaki, Haruo Okado, Gen Sobue, Yanhua Huang, Colleen A McClung
BACKGROUND: Disruptions in circadian rhythms are associated with an increased risk for bipolar disorder. Moreover, studies show that the circadian protein CLOCK (circadian locomotor output cycles kaput) is involved in regulating monoaminergic systems and mood-related behavior. However, the molecular and synaptic mechanisms underlying this relationship remain poorly understood. METHODS: Using ex vivo whole-cell patch-clamp electrophysiology in ClockΔ19 mutant and wild-type mice we characterized alterations in excitatory synaptic transmission, strength, and intrinsic excitability of nucleus accumbens (NAc) neurons...
June 27, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28760987/toll-like-receptor-4-deficiency-alters-nucleus-accumbens-synaptic-physiology-and-drug-reward-behavior
#5
Daniel T Kashima, Brad A Grueter
Behavioral manifestations of drug-seeking behavior are causally linked to alterations of synaptic strength onto nucleus accumbens (NAc) medium spiny neurons (MSN). Although neuron-driven changes in physiology and behavior are well characterized, there is a lack of knowledge of the role of the immune system in mediating such effects. Toll-like receptor 4 (TLR4) is a pattern recognition molecule of the innate immune system, and evidence suggests that it modulates drug-related behavior. Using TLR4 knockout (TLR4...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28760579/survival-of-ipsc-derived-grafts-within-the-striatum-of-immunodeficient-mice-importance-of-developmental-stage-of-both-transplant-and-host-recipient
#6
Colton M Tom, Shahab Younesi, Elana Meer, Catherine Bresee, Marlesa Godoy, Virginia B Mattis
Degeneration of the striatum can occur in multiple disorders with devastating consequences for the patients. Infantile infections with streptococcus, measles, or herpes can cause striatal necrosis associated with dystonia or dyskinesia; and in patients with Huntington's disease the striatum undergoes massive degeneration, leading to behavioral, psychological and movement issues, ultimately resulting in death. Currently, only supportive therapies are available for striatal degeneration. Clinical trials have shown some efficacy using transplantation of fetal-derived primary striatal progenitors...
July 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28757327/differential-electrophysiological-and-morphological-alterations-of-thalamostriatal-and-corticostriatal-projections-in-the-r6-2-mouse-model-of-huntington-s-disease
#7
Anna Parievsky, Cindy Moore, Talia Kamdjou, Carlos Cepeda, Charles K Meshul, Michael S Levine
Huntington's disease (HD) is a fatal genetic disorder characterized by cell death of medium-sized spiny neurons (MSNs) in the striatum, traditionally attributed to excessive glutamate inputs and/or receptor sensitivity. While changes in corticostriatal projections have typically been studied in mouse models of HD, morphological and functional alterations in thalamostriatal projections have received less attention. In this study, an adeno-associated virus expressing channelrhodopsin-2 under the calcium/calmodulin-dependent protein kinase IIα promoter was injected into the sensorimotor cortex or the thalamic centromedian-parafascicular nuclear complex in the R6/2 mouse model of HD, to permit selective activation of corticostriatal or thalamostriatal projections, respectively...
July 27, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28756273/back-to-the-future-circuit-testing-ts-ocd
#8
Frank H Burton
A decade before the rise of optogenetics, the first behavioral "circuit-test" - transgenically modulating the output of a genetically-specified brain circuit element to examine its effect on behavior - was performed. The behaviors emulated in those mice were comorbid tics and compulsions, elicited by a gene borrowed from cholera bacteria and tailored to intracellularly neuropotentiate glutamatergic somatosensory cortical and limbic output neurons of cortico/amygdalo-striato-thalamo-cortical (CSTC) loop circuits...
July 26, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28742811/decreased-rhes-mrna-levels-in-the-brain-of-patients-with-parkinson-s-disease-and-mptp-treated-macaques
#9
Francesco Napolitano, Emily Booth Warren, Sara Migliarini, Daniela Punzo, Francesco Errico, Qin Li, Marie-Laure Thiolat, Angelo Luigi Vescovi, Paolo Calabresi, Erwan Bezard, Micaela Morelli, Christine Konradi, Massimo Pasqualetti, Alessandro Usiello
In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson's disease (PD), Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls (about 200 post-mortem samples)...
2017: PloS One
https://www.readbyqxmd.com/read/28733355/erk-mapk-signaling-is-required-for-pathway-specific-striatal-motor-functions
#10
Scott R Hutton, James M Otis, Erin M Kim, Yashna Lamsal, Garret D Stuber, William D Snider
The ERK/MAPK intracellular signaling pathway is hypothesized to be a key regulator of striatal activity via modulation of synaptic plasticity and gene transcription. However, prior investigations into striatal ERK/MAPK functions have yielded conflicting results. Further, these studies have not delineated the cell type-specific roles of ERK/MAPK signaling due to the reliance on globally-administered pharmacological ERK/MAPK inhibitors and the use of genetic models that only partially reduce total ERK/MAPK activity...
July 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28729439/striatal-gpr88-modulates-foraging-efficiency
#11
Aundrea Rainwater, Elisenda Sanz, Richard D Palmiter, Albert Quintana
The striatum is anatomically and behaviorally implicated in behaviors that promote efficient foraging. To investigate this function, we studied instrumental choice behavior in mice lacking GPR88, a striatum-enriched orphan G-protein-coupled receptor that modulates striatal medium spiny neuron (MSN) excitability. Our results reveal that hungry mice lacking GPR88 (KO mice) were slow to acquire food-reinforced lever-press, but could lever press similar to controls on a progressive-ratio schedule. Both WT and KO mice discriminated between reward and no-reward levers; however, KO mice failed to discriminate based on relative quantity- reward (1 versus 3 food pellets) or effort (3 versus 9 lever presses)...
July 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28720405/persistent-cognitive-and-morphological-alterations-induced-by-repeated-exposure-of-adolescent-rats-to-the-abused-inhalant-toluene
#12
K M Braunscheidel, J T Gass, P J Mulholland, S B Floresco, J J Woodward
While thepsychoactive inhalant toluene causes behavioral effects similarto those produced by other drugs of abuse, the persistent behavioral and anatomical abnormalities induced by toluene exposure are not well known. To mimic human "binge-like" inhalant intoxication, adolescent, male Sprague-Dawley rats were exposed to toluene vapor (5700ppm) twice daily for five consecutive days. These rats remained in their home cages until adulthood (P60), when they were trained in operant boxes to respond to a palatable food reward and then challenged with several different cognitive tasks...
July 15, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28708260/effect-of-optogenetic-manipulation-of-accumbal-medium-spiny-neurons-expressing-dopamine-d2-receptors-in-cocaine-induced-behavioral-sensitization
#13
Byeong Jun Kang, Shelly Sooyun Song, Lei Wen, Ki-Pyo Hong, George J Augustine, Ja-Hyun Baik
Repetitive exposure to addictive drugs causes synaptic modification in the mesocorticolimbic dopamine (DA) system. Dopamine D1 receptors (D1R) or D2 receptors (D2R) expressed in the medium spiny neurons (MSNs) of the nucleus accumbens (NAc) play critical roles in the control of addictive behaviors. Optogenetic activation of D2R-expressing MSNs (D2R-MSNs) in the NAc previously demonstrated that these neurons play a key role in withdrawal-induced plasticity. Here, we examined the effect of optogenetic inhibition of D2R-MSNs in the NAc on cocaine-induced behavioral sensitization...
July 14, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28700108/gpr88-in-a2a-receptor-expressing-neurons-modulates-locomotor-response-to-dopamine-agonists-but-not-sensorimotor-gating
#14
A C Meirsman, A de Kerchove d'Exaerde, B L Kieffer, A-M Ouagazzal
The orphan receptor, GPR88, is emerging as a key player in the pathophysiology of several neuropsychiatric diseases, including psychotic disorders. Knockout (KO) mice lacking GPR88 throughout the brain exhibit many abnormalities relevant to schizophrenia including locomotor hyperactivity, behavioural hypersensitivity to dopaminergic psychostimulants and deficient sensorimotor gating. Here, we used conditional knockout (cKO) mice lacking GPR88 selectively in striatal medium spiny neurons expressing A2A receptor to determine neuronal circuits underlying these phenotypes...
August 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28687229/the-phosphodiesterase-10a-selective-inhibitor-tak-063-induces-c-fos-expression-in-both-direct-and-indirect-pathway-medium-spiny-neurons-and-sub-regions-of-the-medial-prefrontal-cortex-in-rats
#15
Atsushi Nakatani, Sayuri Nakamura, Haruhide Kimura
TAK-063, a selective phosphodiesterase 10A (PDE10A) inhibitor, produces potent antipsychotic-like and pro-cognitive effects in rodents via balanced activation of striatal direct and indirect pathway medium spiny neurons (MSNs). Brain activity modulation by TAK-063 has been characterized using pharmacological magnetic resonance imaging and electroencephalography in animals, revealing modulation of activity in the prefrontal cortex (PFC) where there is little or no PDE10A expression. To understand the specific brain regions and cells affected by TAK-063 in rats, we assessed neural activation in the striatal complex and PFC using immunofluorescence staining to measure c-Fos expression...
July 4, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28676743/differential-alteration-in-expression-of-striatal-gabaar-subunits-in-mouse-models-of-huntington-s-disease
#16
Zhuowei Du, Margot Tertrais, Gilles Courtand, Thierry Leste-Lasserre, Laura Cardoit, Frédérique Masmejean, Christophe Halgand, Yoon H Cho, Maurice Garret
Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor symptoms that are preceded by cognitive deficits and is considered as a disorder that primarily affects forebrain striatal neurons. To gain a better understanding of the molecular and cellular mechanisms associated with disease progression, we analyzed the expression of proteins involved in GABAergic neurotransmission in the striatum of the R6/1 transgenic mouse model. Western blot, quantitative PCR and immunohistochemical analyses were conducted on male R6/1 mice and age-matched wild type littermates...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28667174/erbb4-deletion-from-medium-spiny-neurons-of-the-nucleus-accumbens-core-induces-schizophrenia-like-behaviors-via-elevated-gabaa-receptor-%C3%AE-1-subunit-expression
#17
Hong-Yan Geng, Jing Zhang, Jian-Ming Yang, Yue Li, Ning Wang, Mao Ye, Xiao-Juan Chen, Hong Lian, Xiao-Ming Li
Medium spiny neurons (MSNs), the major GABAergic projection neurons in the striatum, are implicated in many neuropsychiatric diseases such as schizophrenia, but the underlying mechanisms remain unclear. We found that a deficiency in Erbb4, a schizophrenia risk gene, in MSNs of the nucleus accumbens (NAc) core, but not the dorsomedial striatum, markedly induced schizophrenia-like behaviors such as hyperactivity, abnormal marble-burying behavior, damaged social novelty recognition, and impaired sensorimotor gating function in male mice...
August 2, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28659329/shared-motivational-functions-of-ventral-striatum-d1-and-d2-medium-spiny-neurons
#18
Meghan Flanigan, Katherine LeClair
No abstract text is available yet for this article.
June 28, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28656742/long-term-subregion-specific-encoding-of-enhanced-ethanol-intake-by-d1dr-medium-spiny-neurons-of-the-nucleus-accumbens
#19
Rafael Renteria, Tavanna R Buske, Richard A Morrisett
The nucleus accumbens (NAc) is a critical component of the mesocorticolimbic system and is involved in mediating the motivational and reinforcing aspects of ethanol consumption. Chronic intermittent ethanol (CIE) exposure is a reliable model to induce ethanol dependence and increase volitional ethanol consumption in mice. Following a CIE-induced escalation of ethanol consumption, NMDAR (N-methyl-D-aspartate receptor)-dependent long-term depression in D1 dopamine receptor expressing medium spiny neurons of the NAc shell was markedly altered with no changes in plasticity in D1 dopamine receptor medium spiny neurons from the NAc core...
June 28, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28655644/pregnenolone-does-not-interfere-with-the-effects-of-cannabinoids-on-synaptic-transmission-in-the-cerebellum-and-the-nucleus-accumbens
#20
Anna Krohmer, Martin Brehm, Volker Auwärter, Bela Szabo
The steroid hormone pregnenolone attenuates several in vivo behavioural and somatic effects of the phytocannabinoid Δ(9)-tetrahydrocannabinol, and it was suggested that pregnenolone can protect the brain from cannabis intoxication. The primary neuronal cannabinoid action behind most of the behavioural and somatic effects of cannabinoids is presynaptic inhibition of synaptic transmission. Therefore, the hypothesis of the present study was that pregnenolone attenuates the inhibition of synaptic transmission elicited by cannabinoids...
June 24, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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