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https://www.readbyqxmd.com/read/27932959/exposure-to-ketamine-anesthesia-affects-rat-impulsive-behavior
#1
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
#2
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), while 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)...
December 8, 2016: 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27886263/nicotinic-and-opioid-receptor-regulation-of-striatal-dopamine-d2-receptor-mediated-transmission
#10
Aphroditi A Mamaligas, Yuan Cai, Christopher P Ford
In addition to dopamine neuron firing, cholinergic interneurons (ChIs) regulate dopamine release in the striatum via presynaptic nicotinic receptors (nAChRs) on dopamine axon terminals. Synchronous activity of ChIs is necessary to evoke dopamine release through this pathway. The frequency-dependence of disynaptic nicotinic modulation has led to the hypothesis that nAChRs act as a high-pass filter in the dopaminergic microcircuit. Here, we used optogenetics to selectively stimulate either ChIs or dopamine terminals directly in the striatum...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881786/neuronal-dysfunction-in-ipsc-derived-medium-spiny-neurons-from-chorea-acanthocytosis-patients-is-reversed-by-src-kinase-inhibition-and-f-actin-stabilization
#11
Nancy Stanslowsky, Peter Reinhardt, Hannes Glass, Norman Kalmbach, Maximilian Naujock, Niko Hensel, Verena Lübben, Arun Pal, Anna Venneri, Francesca Lupo, Lucia De Franceschi, Peter Claus, Jared Sterneckert, Alexander Storch, Andreas Hermann, Florian Wegner
: Chorea-acanthocytosis (ChAc) is a fatal neurological disorder characterized by red blood cell acanthocytes and striatal neurodegeneration. Recently, severe cell membrane disturbances based on depolymerized cortical actin and an elevated Lyn kinase activity in erythrocytes from ChAc patients were identified. How this contributes to the mechanism of neurodegeneration is still unknown. To gain insight into the pathophysiology, we established a ChAc patient-derived induced pluripotent stem cell model and an efficient differentiation protocol providing a large population of human striatal medium spiny neurons (MSNs), the main target of neurodegeneration in ChAc...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27871668/emerging-role-for-nucleus-accumbens-medium-spiny-neuron-subtypes-in-depression
#12
REVIEW
T Chase Francis, Mary Kay Lobo
The ventral striatum (nucleus accumbens) and its role in mood, reward, and motivation has been the focus of significant research. Despite this interest, little work has addressed cell type-specific distinctions in medium spiny neurons (MSNs), the main projection neurons in the nucleus accumbens and dorsal striatum, and their function in relation to stress and depression. Previous work has shown opposing roles for D1 and D2 receptor MSN subtypes in depression-like outcomes to stress, particularly in regard to repeated neuronal stimulation and excitatory transmission...
September 15, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27860035/a-cell-type-specific-expression-signature-predicts-haploinsufficient-autism-susceptibility-genes
#13
Chaolin Zhang, Yufeng Shen
Recent studies have identified many genes with rare de novo mutations in autism, but a limited number of these have been conclusively established as disease-susceptibility genes due to the lack of recurrence and confounding background mutations. Such extreme genetic heterogeneity severely limits recurrence-based statistical power even in studies with a large sample size. Here, we use cell-type specific expression profiles to differentiate mutations in autism patients from those in unaffected siblings. We report a gene expression signature in different neuronal cell types shared by genes with likely gene-disrupting (LGD) mutations in autism cases...
November 16, 2016: Human Mutation
https://www.readbyqxmd.com/read/27856517/mglur-long-term-depression-regulates-glua2-association-with-copii-vesicles-and-exit-from-the-endoplasmic-reticulum
#14
Joseph E Pick, Latika Khatri, Matheus F Sathler, Edward B Ziff
mGluR long-term depression (mGluR-LTD) is a form of synaptic plasticity induced at excitatory synapses by metabotropic glutamate receptors (mGluRs). mGluR-LTD reduces synaptic strength and is relevant to learning and memory, autism, and sensitization to cocaine; however, the mechanism is not known. Here we show that activation of Group I mGluRs in medium spiny neurons induces trafficking of GluA2 from the endoplasmic reticulum (ER) to the synapse by enhancing GluA2 binding to essential COPII vesicle proteins, Sec23 and Sec13...
November 17, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27853928/d1-and-d2-specific-dopamine-antagonist-modulate-the-caudate-nucleus-neuronal-responses-to-chronic-methylphenidate-exposure
#15
Sidish Venkataraman, Catherine Claussen, Nachum Dafny
The psychostimulant, methylphenidate (MPD), is the first line treatment as a pharmacotherapy to treat behavioral disorders such as attention deficit hyperactivity disorder (ADHD). MPD is commonly misused in non-ADHD (normal) youth and young adults both as a recreational drug and for cognitive enhancing effects to improve their grades. MPD is known to act on the reward circuit; including the caudate nucleus (CN). The CN is comprised of medium spiny neurons containing largely dopamine (DA) D1 and D2 receptors...
November 16, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27818324/the-sigma-1-receptor-mediates-the-beneficial-effects-of-pridopidine-in-a-mouse-model-of-huntington-disease
#16
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/27815415/reduction-of-cocaine-induced-locomotor-effects-by-enriched-environment-is-associated-with-cell-specific-accumulation-of-%C3%AE-fosb-in-striatal-and-cortical-subregions
#17
Audrey Lafragette, Michael T Bardo, Virginie Lardeux, Marcello Solinas, Nathalie Thiriet
BACKGROUND: Early exposure to enriched environments has been shown to decrease the locomotor effects induced by repeated injections of cocaine and modify basal and cocaine-induced total protein levels of the transcription factor ΔFosB in the whole striatum of mice. In this study, we aimed at characterizing whether the profile of ΔFosB accumulation induced by enriched environments and cocaine would be similar or different in terms of brain areas and cell type. METHODS: We used mice expressing the eGFP protein in D1 receptor positive (D1R(+)) neurons to determine whether Δ FosB induced by enriched environment or cocaine injections (5×15 mg/kg) would occur in selective subpopulations of neurons in several subregions of the striatum and prefrontal cortex...
December 8, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27811172/tak-063-a-novel-phosphodiesterase-10a-inhibitor-protects-from-striatal-neurodegeneration-and-ameliorates-behavioral-deficits-in-the-r6-2-mouse-model-of-huntington-s-disease
#18
Akina Harada, Kazunori Suzuki, Haruhide Kimura
Huntington's disease (HD) is characterized by progressive loss of striatal medium spiny neurons (MSNs) that constitute direct and indirect pathways: the indirect pathway MSNs is more vulnerable than the direct pathway MSNs. Impairment of cAMP/cGMP signaling by mutant huntingtin is hypothesized as the molecular mechanism underlying degeneration of MSNs. Phosphodiesterase 10A (PDE10A) is selectively expressed in MSNs and degrades both cAMP and cGMP; thus, PDE10A inhibition can restore impaired cAMP/cGMP signaling...
January 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27793700/suppressive-regulation-of-lateral-inhibition-between-medium-spiny-neurons-via-dopamine-d1-receptors-in-the-rat-nucleus-accumbens-shell
#19
Shuntaro Kohnomi, Katsuko Ebihara, Masayuki Kobayashi
The nucleus accumbens (NAc) shell is closely associated with reward, psychiatric disorders (depression or schizophrenia), and drug abuse. Dopamine, released from the ventral tegmental area, is involved in these physiological functions and pathophysiological changes of NAc shell. Medium spiny neurons (MSNs), which are only GABAergic projection neurons in NAc, also innervate adjacent MSNs, forming the lateral inhibition network. Previous studies demonstrate that dopamine suppresses the lateral inhibition via D2-like (D2 and D3) receptors...
January 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27773571/nf1-is-a-direct-g-protein-effector-essential-for-opioid-signaling-to-ras-in-the-striatum
#20
Keqiang Xie, Lesley A Colgan, Maria T Dao, Brian S Muntean, Laurie P Sutton, Cesare Orlandi, Sanford L Boye, Shannon E Boye, Chien-Cheng Shih, Yuqing Li, Baoji Xu, Roy G Smith, Ryohei Yasuda, Kirill A Martemyanov
It is well recognized that G-protein-coupled receptors (GPCRs) can activate Ras-regulated kinase pathways to produce lasting changes in neuronal function. Mechanisms by which GPCRs transduce these signals and their relevance to brain disorders are not well understood. Here, we identify a major Ras regulator, neurofibromin 1 (NF1), as a direct effector of GPCR signaling via Gβγ subunits in the striatum. We find that binding of Gβγ to NF1 inhibits its ability to inactivate Ras. Deletion of NF1 in striatal neurons prevents the opioid-receptor-induced activation of Ras and eliminates its coupling to Akt-mTOR-signaling pathway...
November 21, 2016: Current Biology: CB
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