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https://www.readbyqxmd.com/read/29038598/male-specific-deficits-in-natural-reward-learning-in-a-mouse-model-of-neurodevelopmental-disorders
#1
N M Grissom, S E McKee, H Schoch, N Bowman, R Havekes, W T O'Brien, E Mahrt, S Siegel, K Commons, C Portfors, T Nickl-Jockschat, T M Reyes, T Abel
Neurodevelopmental disorders, including autism spectrum disorders, are highly male biased, but the underpinnings of this are unknown. Striatal dysfunction has been strongly implicated in the pathophysiology of neurodevelopmental disorders, raising the question of whether there are sex differences in how the striatum is impacted by genetic risk factors linked to neurodevelopmental disorders. Here we report male-specific deficits in striatal function important to reward learning in a mouse model of 16p11.2 hemideletion, a genetic mutation that is strongly associated with the risk of neurodevelopmental disorders, particularly autism and attention-deficit hyperactivity disorder...
October 17, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28985088/modeling-influences-of-dopamine-on-synchronization-behavior-of-striatum
#2
Yüksel Çakir
A network model of striatum that comprises medium spiny neurons (MSNs) and fast spiking interneurons (FSIs) is constructed following the work of Humphries et al. (2009). The dynamic behavior of striatum microcircuit is investigated using a dopamine-modulated modified Izhikevich neuron model. The influences of dopamine on the synchronization behavior of the striatal microcircuit and the dependence on receptor type are investigated with and without time delay. To investigate the role of two types of dopamine receptors, D1 and D2, on the overall activity of the striatum microcircuit, the activities of two groups are considered as disconnected and connected...
October 6, 2017: Network: Computation in Neural Systems
https://www.readbyqxmd.com/read/28977522/psychogenic-stress-activates-c-fos-in-nucleus-accumbens-projecting-neurons-of-the-hippocampal-ventral-subiculum
#3
Witold J Lipski, Sofia M Dibble, Linda Rinaman, Anthony A Grace
Background: The ventral subiculum is known to be activated by the presentation of novel stressors. It has been hypothesized that neuronal ensembles at the ventral aspect of the hippocampal formation are involved in context-dependent processing and can guide the learning of appropriate action selections in response to threatening contexts. Artificial activation of the ventral subiculum can excite medium spiny neurons of the nucleus accumbens and can increase the excitability of mesolimbic dopamine neurons via a polysynaptic pathway through the basal ganglia...
October 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28973852/nucleus-accumbens-feedforward-inhibition-circuit-promotes-cocaine-self-administration
#4
Jun Yu, Yijin Yan, King-Lun Li, Yao Wang, Yanhua H Huang, Nathaniel N Urban, Eric J Nestler, Oliver M Schlüter, Yan Dong
The basolateral amygdala (BLA) sends excitatory projections to the nucleus accumbens (NAc) and regulates motivated behaviors partially by activating NAc medium spiny neurons (MSNs). Here, we characterized a feedforward inhibition circuit, through which BLA-evoked activation of NAc shell (NAcSh) MSNs was fine-tuned by GABAergic monosynaptic innervation from adjacent fast-spiking interneurons (FSIs). Specifically, BLA-to-NAcSh projections predominantly innervated NAcSh FSIs compared with MSNs and triggered action potentials in FSIs preceding BLA-mediated activation of MSNs...
September 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28973132/ikk%C3%AE-and-mutant-huntingtin-interactions-regulate-the-expression-of-il-34-implications-for-microglial-mediated-neurodegeneration-in-hd
#5
Ali Khoshnan, Adam Sabbaugh, Barbara Calamini, Steven A Marinero, Denise E Dunn, Jung Hyun Yoo, Jan Ko, Donald C Lo, Paul H Patterson
Neuronal interleukin-34 (IL-34) promotes the expansion of microglia in the central nervous system-microglial activation and expansion are in turn implicated in the pathogenesis of Huntington's disease (HD). We thus examined whether the accumulation of an amyloidogenic exon-1 fragment of mutant huntingtin (mHTTx1) modulates the expression of IL-34 in dopaminergic neurons derived from a human embryonic stem cell line. We found that mHTTx1 aggregates induce IL-34 production selectively in post-mitotic neurons...
August 14, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28973019/beta-arrestin-1-regulation-of-reward-motivated-behaviors-and-glutamatergic-function
#6
Nitish Mittal, Ani Minasyan, Nicole Romaneschi, Joshua K Hakimian, Gabriel Gonzalez-Fernandez, Ralph Albert, Nina Desai, Ian A Mendez, Timothy Schallert, Sean B Ostlund, Wendy Walwyn
The two highly homologous non-visual arrestins, beta-arrestin 1 and 2, are ubiquitously expressed in the central nervous system, yet knowledge of their disparate roles is limited. While beta-arrestin 2 (βarr2) has been implicated in several aspects of reward-related learning and behavior, very little is known about the behavioral function of beta-arrestin 1 (βarr1). Using mice lacking βarr1, we focused on the role of this scaffolding and signal transduction protein in reward-motivated behaviors and in striatal glutamatergic function...
2017: PloS One
https://www.readbyqxmd.com/read/28966085/distinct-roles-of-ventromedial-versus-ventrolateral-striatal-medium-spiny-neurons-in-reward-oriented-behavior
#7
Iku Tsutsui-Kimura, Akiyo Natsubori, Marina Mori, Kenta Kobayashi, Michael R Drew, Alban de Kerchove d'Exaerde, Masaru Mimura, Kenji F Tanaka
The ventral striatum (VS) is a key brain center regulating reward-oriented behavior [1-4]. The VS can be anatomically divided into medial (VMS) and lateral (VLS) portions based on cortical input patterns. The VMS receives inputs from medial pallium-originated limbic structures (e.g., the medial prefrontal cortex [mPFC]), and the VLS receives inputs from the lateral pallium-originated areas (e.g., the insula) [5, 6]. This anatomical feature led us to hypothesize a functional segregation within the VS in terms of the regulation of reward-oriented behavior...
October 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28956336/regulation-of-striatal-neuron-activity-by-cyclic-nucleotide-signaling-and-phosphodiesterase-inhibition-implications-for-the-treatment-of-parkinson-s-disease
#8
Fernando E Padovan-Neto, Anthony R West
Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the hydrolysis and inactivation of cyclic nucleotides (cAMP/cGMP) in the brain. Several classes of PDE enzymes with distinct tissue distributions, cyclic nucleotide selectivity, and regulatory factors are highly expressed in brain regions subserving cognitive and motor processes known to be disrupted in neurodegenerative diseases such as Parkinson's disease (PD). Furthermore, small-molecule inhibitors of several different PDE family members alter cyclic nucleotide levels and favorably enhance motor performance and cognition in animal disease models...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28956328/current-understanding-of-pde10a-in-the-modulation-of-basal-ganglia-circuitry
#9
Jan-Philip Schülke, Nicholas J Brandon
The basal ganglia are a forebrain network of interconnected nuclei that are involved in action selection, reward circuits and coordinating movement. PDE10A inhibition has been proposed as a novel way to modulate basal ganglia circuitry and to ameliorate symptoms in Huntington's disease, Parkinson's disease and Schizophrenia. However, despite encouraging results from pre-clinical models, PDE10A inhibitors failed to show efficacy as an antipsychotic in several clinical trials. PDE10A is expressed in the medium spiny neurons of the striatum and works to limit cyclic nucleotide signaling in response to modulatory neurotransmitters like dopamine...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28948210/ncs-rapgef2-the-protein-product-of-the-neuronal-rapgef2-gene-is-a-specific-activator-of-d1-dopamine-receptor-dependent-erk-phosphorylation-in-mouse-brain
#10
Sunny Zhihong Jiang, Wenqin Xu, Andrew C Emery, Charles R Gerfen, Maribeth V Eiden, Lee E Eiden
The neuritogenic cAMP sensor (NCS), encoded by the Rapgef2 gene, links cAMP elevation to activation of extracellular signal-regulated kinase (ERK) in neurons and neuroendocrine cells. Transducing human embryonic kidney (HEK)293 cells, which do not express Rapgef2 protein or respond to cAMP with ERK phosphorylation, with a vector encoding a Rapgef2 cDNA reconstituted cAMP-dependent ERK activation. Mutation of a single residue in the cyclic nucleotide-binding domain (CNBD) conserved across cAMP-binding proteins abrogated cAMP-ERK coupling, while deletion of the CNBD altogether resulted in constitutive ERK activation...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28934250/changes-in-striatal-activity-and-functional-connectivity-in-a-mouse-model-of-huntington-s-disease
#11
Magali Cabanas, Fares Bassil, Nicole Mons, Maurice Garret, Yoon H Cho
Hereditary Huntington's disease (HD) is associated with progressive motor, cognitive and psychiatric symptoms. A primary consequence of the HD mutation is the preferential loss of medium spiny projection cells with relative sparing of local interneurons in the striatum. In addition, among GABAergic striatal projection cells, indirect pathway cells expressing D2 dopamine receptors are lost earlier than direct pathway cells expressing D1 receptors. To test in vivo the functional integrity of direct and indirect pathways as well as interneurons in the striatum of male R6/1 transgenic mice, we assessed their c-Fos expression levels induced by a striatal-dependent cognitive task and compared them with age-matched wild-type littermates...
2017: PloS One
https://www.readbyqxmd.com/read/28912680/fyn-signaling-is-compartmentalized-to-dopamine-d1-receptor-expressing-neurons-in-the-dorsal-medial-striatum
#12
Khanhky Phamluong, Emmanuel Darcq, Su Wu, Samuel A Sakhai, Dorit Ron
The tyrosine kinase Fyn plays an important role in synaptic plasticity, learning, and memory. Here we report that Fyn is activated in response to 15 min D1 receptor (D1R) but not D2 receptor (D2R) stimulation specifically in the dorsomedial striatum (DMS) of mice but not in the other substriatal regions, the dorsolateral striatum (DLS), and the nucleus accumbens (NAc). Once activated Fyn phosphorylates its substrate GluN2B, and we show that GluN2B is phosphorylated only in the DMS but not in the other striatal regions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28910740/generation-of-low-gamma-oscillations-in-a-gabaergic-network-model-of-the-striatum
#13
Zhihua Wu, Aike Guo, Xiaodi Fu
Striatal oscillations in the low-gamma frequency range have been consistently recorded in a number of experimental studies. However, whether these rhythms are locally generated in the striatum circuit, which is mainly composed of GABAergic neurons, remains an open question. GABAergic medium spiny projection neurons represent the great majority of striatal neurons, but they fire at very low rates. GABAergic fast-spiking interneurons typically show firing rates that are approximately 10 times higher than those of principal neurons, but they are a very small minority of the total neuronal population...
November 2017: Neural Networks: the Official Journal of the International Neural Network Society
https://www.readbyqxmd.com/read/28894298/molecular-basis-of-dendritic-atrophy-and-activity-in-stress-susceptibility
#14
T C Francis, R Chandra, A Gaynor, P Konkalmatt, S R Metzbower, B Evans, M Engeln, T A Blanpied, M K Lobo
Molecular and cellular adaptations in nucleus accumbens (NAc) medium spiny neurons (MSNs) underlie stress-induced depression-like behavior, but the molecular substrates mediating cellular plasticity and activity in MSN subtypes in stress susceptibility are poorly understood. We find the transcription factor early growth response 3 (EGR3) is increased in D1 receptor containing MSNs of mice susceptible to social defeat stress. Genetic reduction of Egr3 levels in D1-MSNs prevented depression-like outcomes in stress susceptible mice by preventing D1-MSN dendritic atrophy, reduced frequency of excitatory input and altered in vivo activity...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28893927/mutant-huntingtin-inhibits-%C3%AE-b-crystallin-expression-and-impairs-exosome-secretion-from-astrocytes
#15
Yan Hong, Ting Zhao, Xiao-Jiang Li, Shihua Li
In the brain, astrocytes secrete diverse substances that regulate neuronal function and viability. Exosomes, which are vesicles produced through the formation of multivesicular bodies and their subsequent fusion with the plasma membrane, are also released from astrocytes via exocytotic secretion. Astrocytic exosomes carry heat shock proteins that can reduce the cellular toxicity of misfolded proteins and prevent neurodegeneration. Although mutant huntingtin (mHtt) affects multiple functions of astrocytes, it remains unknown whether mHtt impairs the production of exosomes from astrocytes...
September 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28890345/prosapip1-dependent-synaptic-adaptations-in-the-nucleus-accumbens-drive-alcohol-intake-seeking-and-reward
#16
Sophie Laguesse, Nadege Morisot, Jung Hoon Shin, Feng Liu, Martin F Adrover, Samuel A Sakhai, Marcelo F Lopez, Khanhky Phamluong, William C Griffin, Howard C Becker, Kevin J Bender, Veronica A Alvarez, Dorit Ron
The mammalian target of rapamycin complex 1 (mTORC1), a transducer of local dendritic translation, participates in learning and memory processes as well as in mechanisms underlying alcohol-drinking behaviors. Using an unbiased RNA-seq approach, we identified Prosapip1 as a novel downstream target of mTORC1 whose translation and consequent synaptic protein expression are increased in the nucleus accumbens (NAc) of mice excessively consuming alcohol. We demonstrate that alcohol-dependent increases in Prosapip1 levels promote the formation of actin filaments, leading to changes in dendritic spine morphology of NAc medium spiny neurons (MSNs)...
September 27, 2017: Neuron
https://www.readbyqxmd.com/read/28887882/homogeneous-processing-in-the-striatal-direct-and-indirect-pathways-single-body-part-sensitive-type-iib-neurons-may-express-either-dopamine-receptor-d1-or-d2
#17
Kevin R Coffey, Miles Nader, Jasmeet Bawa, Mark O West
Striatal medium spiny projection neurons (MSNs) output through two diverging circuits, the 'direct and indirect pathways' which originate from minimally overlapping populations of MSNs expressing either the dopamine receptor D1 or the dopamine receptor D2. One modern theory of direct and indirect pathway function proposes that activation of direct pathway MSNs facilitates output of desired motor programs, while activation of indirect pathway MSNs inhibits competing motor programs. A separate theory suggests that coordinated timing or synchrony of the direct and indirect pathways is critical for the execution of refined movements...
September 9, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28883788/loss-of-mitochondrial-ndufs4-in-striatal-medium-spiny-neurons-mediates-progressive-motor-impairment-in-a-mouse-model-of-leigh-syndrome
#18
Byron Chen, Jessica Hui, Kelsey S Montgomery, Alejandro Gella, Irene Bolea, Elisenda Sanz, Richard D Palmiter, Albert Quintana
Inability of mitochondria to generate energy leads to severe and often fatal myoencephalopathies. Among these, Leigh syndrome (LS) is one of the most common childhood mitochondrial diseases; it is characterized by hypotonia, failure to thrive, respiratory insufficiency and progressive mental and motor dysfunction, leading to early death. Basal ganglia nuclei, including the striatum, are affected in LS patients. However, neither the identity of the affected cell types in the striatum nor their contribution to the disease has been established...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28881851/the-involvement-of-darpp-32-in-the-pathophysiology-of-schizophrenia
#19
REVIEW
Haitao Wang, Mohd Farhan, Jiangping Xu, Philip Lazarovici, Wenhua Zheng
Schizophrenia is one of the most devastating heterogeneous psychiatric disorders. The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia based on neurochemical evidences of elevated brain striatal dopamine synthesis capacity and increased dopamine release in response to stress. Dopamine and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) is a cytosolic protein highly enriched in the medium spiny neurons of the neostriatum, considered as the most important integrator between the cortical input and the basal ganglia, and associated with motor control...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28872733/cafeteria-diet-induces-neuroplastic-modifications-in-the-nucleus-accumbens-mediated-by-microglia-activation
#20
Miriam Gutiérrez-Martos, Benoit Girard, Sueli Mendonça-Netto, Julie Perroy, Emmanuel Valjent, Rafael Maldonado, Miquel Martin
High-palatable and caloric foods are widely overconsumed due to hedonic mechanisms that prevail over caloric necessities leading to overeating and overweight. The nucleus accumbens (NAc) is a key brain area modulating the reinforcing effects of palatable foods and is crucially involved in the development of eating disorders. We describe that prolonged exposure to high-caloric chocolate cafeteria diet leads to overeating and overweight in mice. NAc functionality was altered in these mice, presenting structural plasticity modifications in medium spiny neurons, increased expression of neuroinflammatory factors and activated microglia, and abnormal responses after amphetamine-induced hyperlocomotion...
September 5, 2017: Addiction Biology
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