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https://www.readbyqxmd.com/read/28101525/untangling-basal-ganglia-network-dynamics-and-function-role-of-dopamine-depletion-and-inhibition-investigated-in-a-spiking-network-model
#1
Mikael Lindahl, Jeanette Hellgren Kotaleski
The basal ganglia are a crucial brain system for behavioral selection, and their function is disturbed in Parkinson's disease (PD), where neurons exhibit inappropriate synchronization and oscillations. We present a spiking neural model of basal ganglia including plausible details on synaptic dynamics, connectivity patterns, neuron behavior, and dopamine effects. Recordings of neuronal activity in the subthalamic nucleus and Type A (TA; arkypallidal) and Type I (TI; prototypical) neurons in globus pallidus externa were used to validate the model...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28089852/dopamine-d1-receptor-agonist-treatment-attenuates-extinction-of-morphine-conditioned-place-preference-while-increasing-dendritic-complexity-in-the-nucleus-accumbens-core
#2
Kendra L Kobrin, Danielle T Arena, Stephen C Heinrichs, Olivia H Nguyen, Gary B Kaplan
The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions...
January 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28065797/characterising-the-developmental-profile-of-hesc-derived-medium-spiny-neuron-progenitors-and-assessing-mature-neuron-function-using-a-crispr-generated-human-darpp-32-wt-egfp-amp-reporter-line
#3
C P J Hunt, C W Pouton, J M Haynes
In the developing ventral telencephalon, cells of the lateral ganglionic eminence (LGE) give rise to all medium spiny neurons (MSNs). This development occurs in response to a highly orchestrated series of morphogenetic stimuli that pattern the resultant neurons as they develop. Striatal MSNs are characterised by expression of dopamine receptors, dopamine-and cyclic AMP-regulated phosphoprotein (DARPP32) and the neurotransmitter GABA. In this study, we demonstrate that fine tuning WNT and SHH signaling early in human embryonic stem cell differentiation can induce a subpallial progenitor molecular profile...
January 5, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28052701/potential-for-targeting-dopamine-darpp-32-signaling-in-neuropsychiatric-and-neurodegenerative-disorders
#4
Akinori Nishi, Takahide Shuto
Alterations in dopamine neurotransmission has been implicated in pathophysiology of neuropsychiatric and neurodegenerative disorders, and DARPP-32 plays a pivotal role in dopamine neurotransmission. DARPP-32 likely influences dopamine-mediated behaviors in animal models of neuropsychiatric and neurodegenerative disorders and therapeutic effects of pharmacological treatment. Areas covered: We will review animal studies on the biochemical and behavioral roles of DARPP-32 in drug addiction, schizophrenia and Parkinson's disease...
January 13, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28042091/novel-pde10a-transcript-diversity-in-the-human-striatum-insights-into-gene-complexity-conservation-and-regulation
#5
Courtney M MacMullen, Mohammad Fallahi, Ronald L Davis
PDE10A is a cAMP/cGMP phosphodiesterase important in signal transduction within medium spiny neurons of the human striatum. This gene region has been associated with bipolar disorder via case-control and linkage studies. The three most studied human PDE10A isoforms differ in both their N-termini and trafficking within the cell with PDE10A2 found predominantly at the plasma membrane and PDE10A1 and PDE10A19 remaining primarily within the cytosol. RNA-sequencing and 5' RLM-RACE studies of the human putamen and caudate nucleus revealed 16 new exons and 12 novel transcripts of PDE10A, 3 of which are predicted to produce proteins with unique N-termini...
December 29, 2016: Gene
https://www.readbyqxmd.com/read/28041956/basal-ganglia-dysfunction-contributes-to-physical-inactivity-in-obesity
#6
Danielle M Friend, Kavya Devarakonda, Timothy J O'Neal, Miguel Skirzewski, Ioannis Papazoglou, Alanna R Kaplan, Jeih-San Liow, Juen Guo, Sushil G Rane, Marcelo Rubinstein, Veronica A Alvarez, Kevin D Hall, Alexxai V Kravitz
Obesity is associated with physical inactivity, which exacerbates the health consequences of weight gain. However, the mechanisms that mediate this association are unknown. We hypothesized that deficits in dopamine signaling contribute to physical inactivity in obesity. To investigate this, we quantified multiple aspects of dopamine signaling in lean and obese mice. We found that D2-type receptor (D2R) binding in the striatum, but not D1-type receptor binding or dopamine levels, was reduced in obese mice. Genetically removing D2Rs from striatal medium spiny neurons was sufficient to reduce motor activity in lean mice, whereas restoring Gi signaling in these neurons increased activity in obese mice...
December 20, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28025093/varenicline-improves-motor-and-cognitive-deficits-and-decreases-depressive-like-behaviour-in-late-stage-yac128-mice
#7
Ailsa L McGregor, Gary D'Souza, Donghyo Kim, Malcolm D Tingle
OBJECTIVE: Studies in the post mortem human brain and in genetic mouse model suggest that dysfunctional cholinergic neurotransmission, through a loss of agonist rather than receptors may be a significant contributing factor to HD pathology. If correct, pharmacological replacement may therefore be a potential treatment strategy. We have investigated whether chronic administration of the selective nicotinic partial agonist varenicline improved motor, cognitive and affective symptoms in a transgenic mouse model of Huntington's disease...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28017799/x-linked-dystonia-parkinsonism-patient-cells-exhibit-altered-signaling-via-nuclear-factor-kappa-b
#8
Christine A Vaine, David Shin, Christina Liu, William Hendriks, Jyotsna Dhakal, Kyle Shin, Nutan Sharma, Cristopher Bragg
X-linked Dystonia-Parkinsonism (XDP) is a progressive neurodegenerative disease involving the loss of medium spiny neurons within the striatum. An XDP-specific haplotype has been identified, consisting of seven sequence variants which cluster around the human TAF1 gene, but a direct relationship between any of these variants and disease pathogenesis has not yet been demonstrated. Because the pathogenic gene lesion remains unclear, it has been difficult to predict cellular pathways which are affected in XDP cells...
December 22, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27993521/trafficking-of-calcium-permeable-and-calcium-impermeable-ampa-receptors-in-nucleus-accumbens-medium-spiny-neurons-co-cultured-with-prefrontal-cortex-neurons
#9
Craig T Werner, Conor H Murray, Jeremy M Reimers, Niravkumar M Chauhan, Kenneth K Y Woo, Hanna M Molla, Jessica A Loweth, Marina E Wolf
AMPA receptor (AMPAR) transmission onto medium spiny neurons (MSNs) of the adult rat nucleus accumbens (NAc) is normally dominated by GluA2-containing, Ca(2+)-impermeable AMPAR (CI-AMPARs). However, GluA2-lacking, Ca(2+)-permeable AMPA receptors (CP-AMPARs) accumulate after prolonged withdrawal from extended-access cocaine self-administration and thereafter their activation is required for the intensified (incubated) cue-induced cocaine craving that characterizes prolonged withdrawal from such regimens. These findings suggest the existence of mechanisms in NAc MSNs that differentially regulate CI-AMPARs and CP-AMPARs...
December 16, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27956068/axial-levodopa-induced-dyskinesias-and-neuronal-activity-in-the-dorsal-striatum
#10
Stephanie L Alberico, Young-Cho Kim, Tomas Lence, Nandakumar S Narayanan
Levodopa-induced dyskinesias are abnormal involuntary movements that limit the effectiveness of treatments for Parkinson's disease. Although dyskinesias involve the striatum, it is unclear how striatal neurons are involved in dyskinetic movements. Here we record from striatal neurons in mice during levodopa-induced axial dyskinesias. We developed an automated 3-dimensional motion tracking system to capture the development of axial dyskinesias at ∼10ms resolution, and correlated these movements with neuronal activity of striatal medium spiny neurons and fast-spiking interneurons...
December 9, 2016: Neuroscience
https://www.readbyqxmd.com/read/27939396/a-role-for-peroxisome-proliferator-activated-receptor-gamma-coactivator-1%C3%AE-in-nucleus-accumbens-neuron-subtypes-in-cocaine-action
#11
Ramesh Chandra, Michel Engeln, T Chase Francis, Prasad Konkalmatt, Dipal Patel, Mary Kay Lobo
BACKGROUND: Molecules critically involved in cocaine behavioral plasticity are known to regulate and interact with peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). In addition, the PGC-1α promoter has binding sites for early growth response 3 (Egr3), which plays a dynamic role in cocaine action in nucleus accumbens (NAc) medium spiny neuron (MSN) subtypes, those enriched in dopamine receptor D1 (D1-MSN) versus D2 (D2-MSN). However, the role of PGC-1α in NAc in cocaine action is unknown...
October 28, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27932959/exposure-to-ketamine-anesthesia-affects-rat-impulsive-behavior
#12
António Melo, Hugo Leite-Almeida, Clara Ferreira, Nuno Sousa, José M Pêgo
Introduction: Ketamine is a general anesthetic (GA) that activates several neurotransmitter pathways in various part of the brain. The acute effects as GA are the most well-known and sought-after: to induce loss of responsiveness and to produce immobility during invasive procedures. However, there is a concern that repeated exposure might induce behavioral changes that could outlast their acute effect. Most research in this field describes how GA affects cognition and memory. Our work is to access if general anesthesia with ketamine can disrupt the motivational behavior trait, more specifically measuring impulsive behavior...
2016: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/27929113/a-feedforward-inhibitory-circuit-mediated-by-cb1-expressing-fast-spiking-interneurons-in-the-nucleus-accumbens
#13
William J Wright, Oliver M Schlüter, Yan Dong
The nucleus accumbens (NAc) gates motivated behaviors through the functional output of principle medium spiny neurons (MSNs), whereas dysfunctional output of NAc MSNs contributes to a variety of psychiatric disorders. Fast-spiking interneurons (FSIs) are sparsely distributed throughout the NAc, forming local feedforward inhibitory circuits. It remains elusive how FSI-based feedforward circuits regulate the output of NAc MSNs. Here, we investigated a distinct subpopulation of NAc FSIs that express the cannabinoid receptor type-1 (CB1)...
January 4, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27927785/dopaminergic-treatment-weakens-medium-spiny-neuron-collateral-inhibition-in-the-parkinsonian-striatum
#14
Wei Wei, Shengyuan Ding, Fu-Ming Zhou
The striatal medium spiny neurons (MSNs) are critical to both motor and cognitive functions. A potential regulator of MSN activity is the GABAergic collateral axonal input from neighboring MSNs. These collateral axon terminals are further under the regulation of presynaptic dopamine (DA) receptors that may become dysfunctional when the intense striatal DA innervation is lost in Parkinson's disease (PD). We show here that DA D1 receptor-expressing MSNs (D1-MSNs) and D2 receptor-expressing MSNs (D2-MSNs) each formed high rate, one-way collateral connections with a homotypic preference in both normal and DA-denervated mouse striatum...
December 7, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27922607/endocytosis-following-dopamine-d2-receptor-activation-is-critical-for-neuronal-activity-and-dendritic-spine-formation-via-rabex-5-pdgfr%C3%AE-signaling-in-striatopallidal-medium-spiny-neurons
#15
N Shioda, Y Yabuki, Y Wang, M Uchigashima, T Hikida, T Sasaoka, H Mori, M Watanabe, M Sasahara, K Fukunaga
Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disorders, making those receptors targets for antipsychotic drugs. Here, we report that novel signaling through the intracellularly localized D2R long isoform (D2LR) elicits extracellular signal-regulated kinase (ERK) activation and dendritic spine formation through Rabex-5/platelet-derived growth factor receptor-β (PDGFRβ)-mediated endocytosis in mouse striatum. We found that D2LR directly binds to and activates Rabex-5, promoting early-endosome formation...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27920147/accumbens-nnos-interneurons-regulate-cocaine-relapse
#16
Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Neringa M Stankeviciute, Rachel Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
: Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine-seeking result from glutamate spillover initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27914882/representation-of-the-body-in-the-lateral-striatum-of-the-freely-moving-rat-fast-spiking-interneurons-respond-to-stimulation-of-individual-body-parts
#17
Julianna Kulik, Anthony Pawlak, Manraj Kalkat, Kevin Coffey, Mark O West
: Numerous studies have shown that certain types of striatal interneurons play a crucial role in selection and regulation of striatal output. Striatal Fast-Spiking Interneurons (FSIs) are parvalbumin positive, GABAergic interneurons that constitute less than 1% of the total striatal population. It is becoming increasingly evident that these sparsely distributed neurons exert a strong inhibitory effect on Medium Spiny projection Neurons (MSNs). MSNs in lateral striatum receive direct synaptic input from regions of cortex representing discrete body parts, and show phasic increases in activity during touch or movement of specific body parts...
November 30, 2016: Brain Research
https://www.readbyqxmd.com/read/27912066/cell-type-specific-optical-recording-of-membrane-voltage-dynamics-in-freely-moving-mice
#18
Jesse D Marshall, Jin Zhong Li, Yanping Zhang, Yiyang Gong, François St-Pierre, Michael Z Lin, Mark J Schnitzer
Electrophysiological field potential dynamics are of fundamental interest in basic and clinical neuroscience, but how specific cell types shape these dynamics in the live brain is poorly understood. To empower mechanistic studies, we created an optical technique, TEMPO, that records the aggregate trans-membrane voltage dynamics of genetically specified neurons in freely behaving mice. TEMPO has >10-fold greater sensitivity than prior fiber-optic techniques and attains the noise minimum set by quantum mechanical photon shot noise...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27909104/loss-of-plasticity-in-the-d2-accumbens-pallidal-pathway-promotes-cocaine-seeking
#19
J A Heinsbroek, D N Neuhofer, W C Griffin, G S Siegel, A-C Bobadilla, Y M Kupchik, P W Kalivas
Distinct populations of D1- and D2-dopamine receptor expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, while activity in D2-MSNs inhibits motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903793/the-serotonin-5-ht2c-receptor-and-the-non-addictive-nature-of-classic-hallucinogens
#20
REVIEW
Clinton E Canal, Kevin S Murnane
Classic hallucinogens share pharmacology as serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptor agonists. Unique among most other Schedule 1 drugs, they are generally non-addictive and can be effective tools in the treatment of addiction. Mechanisms underlying these attributes are largely unknown. However, many preclinical studies show that 5-HT2C agonists counteract the addictive effects of drugs from several classes, suggesting this pharmacological property of classic hallucinogens may be significant. Drawing from a comprehensive analysis of preclinical behavior, neuroanatomy, and neurochemistry studies, this review builds rationale for this hypothesis, and also proposes a testable, neurobiological framework...
November 15, 2016: Journal of Psychopharmacology
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