NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control.

Abstract:

:The striatum plays a fundamental role in motor learning and reward-related behaviors that are synergistically shaped by populations of D1 dopamine receptor (D1R)- and D2 dopamine receptor (D2R)-expressing medium spiny neurons (MSNs). How various neurotransmitter inputs converging on common intracellular pathways are parsed out to regulate distinct behavioral outcomes in a neuron-specific manner is poorly understood. Here, we reveal that distinct contributions of D1R-MSNs and D2R-MSNs towards reward and motor behaviors are delineated by the multifaceted signaling protein neurofibromin 1 (NF1). Using genetic mouse models, we show that NF1 in D1R-MSN modulates opioid reward, whereas loss of NF1 in D2R-MSNs delays motor learning by impeding the formation and consolidation of repetitive motor sequences. We found that motor learning deficits upon NF1 loss were associated with the disruption in dopamine signaling to cAMP in D2R-MSN. Restoration of cAMP levels pharmacologically or chemogenetically rescued the motor learning deficits seen upon NF1 loss in D2R-MSN. Our findings illustrate that multiplex signaling capabilities of MSNs are deployed at the level of intracellular pathways to achieve cell-specific control over behavioral outcomes.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Sutton LP,Muntean BS,Ostrovskaya O,Zucca S,Dao M,Orlandi C,Song C,Xie K,Martemyanov KA

doi

10.1371/journal.pbio.3000477

subject

Has Abstract

pub_date

2019-10-10 00:00:00

pages

e3000477

issue

10

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-19-00484

journal_volume

17

pub_type

杂志文章
  • Activity patterns in mammals: Circadian dominance challenged.

    abstract::The evidence that diel patterns of physiology and behaviour in mammals are governed by circadian 'clocks' is based almost entirely on studies of nocturnal rodents. The emergent circadian paradigm, however, neglects the roles of energy metabolism and alimentary function (feeding and digestion) as determinants of activi...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000360

    authors: Hazlerigg DG,Tyler NJC

    更新日期:2019-07-15 00:00:00

  • MooSciTIC: Training of trainers in West African research and higher education.

    abstract::The MooSciTIC project is a capacity-building initiative targeting West African research scientists and higher education teachers. The project aimed to improve the self-reliance of researchers and upgrade research practices by providing on-site summer schools on trans-disciplinary topics such as scientific writing, com...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000312

    authors: Atindehou M,Adéoti K,Loko LEY,Beulé T,Paradis E,Djedatin G,Tranchant-Dubreuil C,Sabot F,Lagnika L,Jaligot E

    更新日期:2019-06-07 00:00:00

  • Sonic Hedgehog promotes tumor cell survival by inhibiting CDON pro-apoptotic activity.

    abstract::The Hedgehog signaling is a determinant pathway for tumor progression. However, while inhibition of the Hedgehog canonical pathway-Patched-Smoothened-Gli-has proved efficient in human tumors with activating mutations in this pathway, recent clinical data have failed to show any benefit in other cancers, even though So...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001623

    authors: Delloye-Bourgeois C,Gibert B,Rama N,Delcros JG,Gadot N,Scoazec JY,Krauss R,Bernet A,Mehlen P

    更新日期:2013-01-01 00:00:00

  • High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography.

    abstract::Mycobacterium tuberculosis infects one third of the human world population and kills someone every 15 seconds. For more than a century, scientists and clinicians have been distinguishing between the human- and animal-adapted members of the M. tuberculosis complex (MTBC). However, all human-adapted strains of MTBC have...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0060311

    authors: Hershberg R,Lipatov M,Small PM,Sheffer H,Niemann S,Homolka S,Roach JC,Kremer K,Petrov DA,Feldman MW,Gagneux S

    更新日期:2008-12-16 00:00:00

  • BEAF regulates cell-cycle genes through the controlled deposition of H3K9 methylation marks into its conserved dual-core binding sites.

    abstract::Chromatin insulators/boundary elements share the ability to insulate a transgene from its chromosomal context by blocking promiscuous enhancer-promoter interactions and heterochromatin spreading. Several insulating factors target different DNA consensus sequences, defining distinct subfamilies of insulators. Whether e...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0060327

    authors: Emberly E,Blattes R,Schuettengruber B,Hennion M,Jiang N,Hart CM,Käs E,Cuvier O

    更新日期:2008-12-23 00:00:00

  • EpCAM ectodomain EpEX is a ligand of EGFR that counteracts EGF-mediated epithelial-mesenchymal transition through modulation of phospho-ERK1/2 in head and neck cancers.

    abstract::Head and neck squamous cell carcinomas (HNSCCs) are characterized by outstanding molecular heterogeneity that results in severe therapy resistance and poor clinical outcome. Inter- and intratumoral heterogeneity in epithelial-mesenchymal transition (EMT) was recently revealed as a major parameter of poor clinical outc...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2006624

    authors: Pan M,Schinke H,Luxenburger E,Kranz G,Shakhtour J,Libl D,Huang Y,Gaber A,Pavšič M,Lenarčič B,Kitz J,Jakob M,Schwenk-Zieger S,Canis M,Hess J,Unger K,Baumeister P,Gires O

    更新日期:2018-09-27 00:00:00

  • An unexpected sequence of events: mismatch detection in the human hippocampus.

    abstract::The ability to identify and react to novelty within the environment is fundamental to survival. Computational models emphasize the potential role of the hippocampus in novelty detection, its unique anatomical circuitry making it ideally suited to act as a comparator between past and present experience. The hippocampus...

    journal_title:PLoS biology

    pub_type: 杂志文章,随机对照试验

    doi:10.1371/journal.pbio.0040424

    authors: Kumaran D,Maguire EA

    更新日期:2006-11-01 00:00:00

  • Parallel evolution of the genetic code in arthropod mitochondrial genomes.

    abstract::The genetic code provides the translation table necessary to transform the information contained in DNA into the language of proteins. In this table, a correspondence between each codon and each amino acid is established: tRNA is the main adaptor that links the two. Although the genetic code is nearly universal, sever...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0040127

    authors: Abascal F,Posada D,Knight RD,Zardoya R

    更新日期:2006-05-01 00:00:00

  • Correction: Tracking Resilience to Infections by Mapping Disease Space.

    abstract::[This corrects the article DOI: 10.1371/journal.pbio.1002436.]. ...

    journal_title:PLoS biology

    pub_type: 已发布勘误

    doi:10.1371/journal.pbio.1002494

    authors: PLOS Biology Staff.

    更新日期:2016-06-08 00:00:00

  • Inhibition of Notch signaling rescues cardiovascular development in Kabuki Syndrome.

    abstract::Kabuki Syndrome patients have a spectrum of congenital disorders, including congenital heart defects, the primary determinant of mortality. Seventy percent of Kabuki Syndrome patients have mutations in the histone methyl-transferase KMT2D. However, the underlying mechanisms that drive these congenital disorders are un...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000087

    authors: Serrano MLA,Demarest BL,Tone-Pah-Hote T,Tristani-Firouzi M,Yost HJ

    更新日期:2019-09-03 00:00:00

  • Birds, blooms, and evolving diversity.

    abstract::In this Open Highlight, Senior Editor Lauren Richardson features exciting new Open Access research into how species evolve their characteristic traits. ...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.3000020

    authors: Richardson LA

    更新日期:2018-10-04 00:00:00

  • Genomic insights into methanotrophy: the complete genome sequence of Methylococcus capsulatus (Bath).

    abstract::Methanotrophs are ubiquitous bacteria that can use the greenhouse gas methane as a sole carbon and energy source for growth, thus playing major roles in global carbon cycles, and in particular, substantially reducing emissions of biologically generated methane to the atmosphere. Despite their importance, and in contra...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0020303

    authors: Ward N,Larsen Ø,Sakwa J,Bruseth L,Khouri H,Durkin AS,Dimitrov G,Jiang L,Scanlan D,Kang KH,Lewis M,Nelson KE,Methé B,Wu M,Heidelberg JF,Paulsen IT,Fouts D,Ravel J,Tettelin H,Ren Q,Read T,DeBoy RT,Seshadri R,S

    更新日期:2004-10-01 00:00:00

  • Representations of Value in the Brain: An Embarrassment of Riches?

    abstract::Over the past two decades, neuroscientists have increasingly turned their attention to the question of how the brain implements decisions between differently valued options. This emerging field, called neuroeconomics, has made quick progress in identifying a plethora of brain areas that track or are modulated by rewar...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002174

    authors: Stott JJ,Redish AD

    更新日期:2015-06-18 00:00:00

  • Compensatory growth impairs adult cognitive performance.

    abstract::Several studies have demonstrated that poor early nutrition, followed by growth compensation, can have negative consequences later in life. However, it remains unclear whether this is attributable to the nutritional deficit itself or a cost of compensatory growth. This distinction is important to our understanding bot...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0040251

    authors: Fisher MO,Nager RG,Monaghan P

    更新日期:2006-07-01 00:00:00

  • Role of a novel PH-kinase domain interface in PKB/Akt regulation: structural mechanism for allosteric inhibition.

    abstract::Protein kinase B (PKB/Akt) belongs to the AGC superfamily of related serine/threonine protein kinases. It is a key regulator downstream of various growth factors and hormones and is involved in malignant transformation and chemo-resistance. Full-length PKB protein has not been crystallised, thus studying the molecular...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000017

    authors: Calleja V,Laguerre M,Parker PJ,Larijani B

    更新日期:2009-01-20 00:00:00

  • Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth in developing mice.

    abstract::Catch-up growth after insults to growing organs is paramount to achieving robust body proportions. In fly larvae, injury to individual tissues is followed by local and systemic compensatory mechanisms that allow the damaged tissue to regain normal proportions with other tissues. In vertebrates, local catch-up growth h...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2005086

    authors: Roselló-Díez A,Madisen L,Bastide S,Zeng H,Joyner AL

    更新日期:2018-06-26 00:00:00

  • Ultrasonic songs of male mice.

    abstract::Previously it was shown that male mice, when they encounter female mice or their pheromones, emit ultrasonic vocalizations with frequencies ranging over 30-110 kHz. Here, we show that these vocalizations have the characteristics of song, consisting of several different syllable types, whose temporal sequencing include...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0030386

    authors: Holy TE,Guo Z

    更新日期:2005-12-01 00:00:00

  • Ligands for pheromone-sensing neurons are not conformationally activated odorant binding proteins.

    abstract::Pheromones form an essential chemical language of intraspecific communication in many animals. How olfactory systems recognize pheromonal signals with both sensitivity and specificity is not well understood. An important in vivo paradigm for this process is the detection mechanism of the sex pheromone (Z)-11-octadecen...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001546

    authors: Gomez-Diaz C,Reina JH,Cambillau C,Benton R

    更新日期:2013-01-01 00:00:00

  • The homeostatic dynamics of feeding behaviour identify novel mechanisms of anorectic agents.

    abstract::Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analys...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000482

    authors: McGrath TM,Spreckley E,Rodriguez AF,Viscomi C,Alamshah A,Akalestou E,Murphy KG,Jones NS

    更新日期:2019-12-05 00:00:00

  • Distinct mammalian precursors are committed to generate neurons with defined dendritic projection patterns.

    abstract::The mechanisms that regulate how dendrites target different neurons to establish connections with specific cell types remain largely unknown. In particular, the formation of cell-type-specific connectivity during postnatal neurogenesis could be either determined by the local environment of the mature neuronal circuit ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0050300

    authors: Kelsch W,Mosley CP,Lin CW,Lois C

    更新日期:2007-11-01 00:00:00

  • Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling.

    abstract::Recent evidence suggests that many malignancies, including breast cancer, are driven by a cellular subcomponent that displays stem cell-like properties. The protein phosphatase and tensin homolog (PTEN) is inactivated in a wide range of human cancers, an alteration that is associated with a poor prognosis. Because PTE...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000121

    authors: Korkaya H,Paulson A,Charafe-Jauffret E,Ginestier C,Brown M,Dutcher J,Clouthier SG,Wicha MS

    更新日期:2009-06-02 00:00:00

  • Identification of traits and functional connectivity-based neurotraits of chronic pain.

    abstract::Psychological and personality factors, socioeconomic status, and brain properties all contribute to chronic pain but have essentially been studied independently. Here, we administered a broad battery of questionnaires to patients with chronic back pain (CBP) and collected repeated sessions of resting-state functional ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000349

    authors: Vachon-Presseau E,Berger SE,Abdullah TB,Griffith JW,Schnitzer TJ,Apkarian AV

    更新日期:2019-08-20 00:00:00

  • Research chimpanzees may get a break.

    abstract::A recent report by the Institute of Medicine leaves few urgent reasons standing for the continued use of chimpanzees in biomedical research. It is high time to think about their retirement, Frans de Waal argues, without neglecting prospects for non-invasive research on behavior, cognition, and genetics. ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001291

    authors: de Waal FB

    更新日期:2012-01-01 00:00:00

  • A20-deficient mast cells exacerbate inflammatory responses in vivo.

    abstract::Mast cells are implicated in the pathogenesis of inflammatory and autoimmune diseases. However, this notion based on studies in mast cell-deficient mice is controversial. We therefore established an in vivo model for hyperactive mast cells by specifically ablating the NF-κB negative feedback regulator A20. While A20 d...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001762

    authors: Heger K,Fierens K,Vahl JC,Aszodi A,Peschke K,Schenten D,Hammad H,Beyaert R,Saur D,van Loo G,Roers A,Lambrecht BN,Kool M,Schmidt-Supprian M

    更新日期:2014-01-01 00:00:00

  • The interaction between a sexually transferred steroid hormone and a female protein regulates oogenesis in the malaria mosquito Anopheles gambiae.

    abstract::Molecular interactions between male and female factors during mating profoundly affect the reproductive behavior and physiology of female insects. In natural populations of the malaria mosquito Anopheles gambiae, blood-fed females direct nutritional resources towards oogenesis only when inseminated. Here we show that ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001695

    authors: Baldini F,Gabrieli P,South A,Valim C,Mancini F,Catteruccia F

    更新日期:2013-10-01 00:00:00

  • Premitotic assembly of human CENPs -T and -W switches centromeric chromatin to a mitotic state.

    abstract::Centromeres are differentiated chromatin domains, present once per chromosome, that direct segregation of the genome in mitosis and meiosis by specifying assembly of the kinetochore. They are distinct genetic loci in that their identity in most organisms is determined not by the DNA sequences they are associated with,...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001082

    authors: Prendergast L,van Vuuren C,Kaczmarczyk A,Doering V,Hellwig D,Quinn N,Hoischen C,Diekmann S,Sullivan KF

    更新日期:2011-06-01 00:00:00

  • A new type of Na(+)-driven ATP synthase membrane rotor with a two-carboxylate ion-coupling motif.

    abstract::The anaerobic bacterium Fusobacterium nucleatum uses glutamate decarboxylation to generate a transmembrane gradient of Na⁺. Here, we demonstrate that this ion-motive force is directly coupled to ATP synthesis, via an F₁F₀-ATP synthase with a novel Na⁺ recognition motif, shared by other human pathogens. Molecular model...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001596

    authors: Schulz S,Iglesias-Cans M,Krah A,Yildiz O,Leone V,Matthies D,Cook GM,Faraldo-Gómez JD,Meier T

    更新日期:2013-01-01 00:00:00

  • Promoter sequence determines the relationship between expression level and noise.

    abstract::The ability of cells to accurately control gene expression levels in response to extracellular cues is limited by the inherently stochastic nature of transcriptional regulation. A change in transcription factor (TF) activity results in changes in the expression of its targets, but the way in which cell-to-cell variabi...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001528

    authors: Carey LB,van Dijk D,Sloot PM,Kaandorp JA,Segal E

    更新日期:2013-01-01 00:00:00

  • Identification of molecular determinants that govern distinct STIM2 activation dynamics.

    abstract::The endoplasmic reticulum (ER) Ca2+ sensors stromal interaction molecule 1 (STIM1) and STIM2, which connect ER Ca2+ depletion with extracellular Ca2+ influx, are crucial for the maintenance of Ca2+ homeostasis in mammalian cells. Despite the recent progress in unraveling the role of STIM2 in Ca2+ signaling, the mechan...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.2006898

    authors: Zheng S,Ma G,He L,Zhang T,Li J,Yuan X,Nguyen NT,Huang Y,Zhang X,Gao P,Nwokonko R,Gill DL,Dong H,Zhou Y,Wang Y

    更新日期:2018-11-16 00:00:00

  • The "backdoor pathway" of androgen synthesis in human male sexual development.

    abstract::Mammalian sex determination (male versus female) is largely controlled by genes, whereas sex differentiation (development of reproductive structures) is largely controlled by hormones. Work in the 20th century indicated that female external anatomy was a "default" pathway of development not requiring steroids, whereas...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.3000198

    authors: Miller WL,Auchus RJ

    更新日期:2019-04-03 00:00:00