IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0009348.html
   My bibliography  Save this article

Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance

Author

Listed:
  • Alessandro Bertolino
  • Paolo Taurisano
  • Nicola Marco Pisciotta
  • Giuseppe Blasi
  • Leonardo Fazio
  • Raffaella Romano
  • Barbara Gelao
  • Luciana Lo Bianco
  • Madia Lozupone
  • Annabella Di Giorgio
  • Grazia Caforio
  • Fabio Sambataro
  • Artor Niccoli-Asabella
  • Audrey Papp
  • Gianluca Ursini
  • Lorenzo Sinibaldi
  • Teresa Popolizio
  • Wolfgang Sadee
  • Giuseppe Rubini

Abstract

Background: Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Methods: Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Results: Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Conclusions: Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

Suggested Citation

  • Alessandro Bertolino & Paolo Taurisano & Nicola Marco Pisciotta & Giuseppe Blasi & Leonardo Fazio & Raffaella Romano & Barbara Gelao & Luciana Lo Bianco & Madia Lozupone & Annabella Di Giorgio & Grazi, 2010. "Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance," PLOS ONE, Public Library of Science, vol. 5(2), pages 1-10, February.
  • Handle: RePEc:plo:pone00:0009348
    DOI: 10.1371/journal.pone.0009348
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0009348
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0009348&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0009348?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alessandro Usiello & Ja-Hyun Baik & Françoise Rougé-Pont & Roberto Picetti & Andrée Dierich & Marianne LeMeur & Pier Vincenzo Piazza & Emiliana Borrelli, 2000. "Distinct functions of the two isoforms of dopamine D2 receptors," Nature, Nature, vol. 408(6809), pages 199-203, November.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Leonardo Sportelli & Daniel P. Eisenberg & Roberta Passiatore & Enrico D’Ambrosio & Linda A. Antonucci & Jasmine S. Bettina & Qiang Chen & Aaron L. Goldman & Michael D. Gregory & Kira Griffiths & Thom, 2024. "Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Katarzyna Świtała & Aleksandra Bojarczuk & Jacek Hajto & Marcin Piechota & Maciej Buryta & Agata Leońska-Duniec, 2022. "Impact of the DRD2 Polymorphisms on the Effectiveness of the Training Program," IJERPH, MDPI, vol. 19(9), pages 1-14, April.
    2. Toshikazu Sasabe & Shoichi Ishiura, 2010. "Alcoholism and Alternative Splicing of Candidate Genes," IJERPH, MDPI, vol. 7(4), pages 1-19, March.
    3. Ya-Qiang Zhang & Wei-Peng Lin & Li-Ping Huang & Bing Zhao & Cheng-Cheng Zhang & Dong-Min Yin, 2021. "Dopamine D2 receptor regulates cortical synaptic pruning in rodents," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    4. Agnieszka Boroń & Małgorzata Śmiarowska & Anna Grzywacz & Krzysztof Chmielowiec & Jolanta Chmielowiec & Jolanta Masiak & Tomasz Pawłowski & Dariusz Larysz & Andrzej Ciechanowicz, 2022. "Association of Polymorphism within the Putative miRNA Target Site in the 3′UTR Region of the DRD2 Gene with Neuroticism in Patients with Substance Use Disorder," IJERPH, MDPI, vol. 19(16), pages 1-21, August.
    5. Leonardo Sportelli & Daniel P. Eisenberg & Roberta Passiatore & Enrico D’Ambrosio & Linda A. Antonucci & Jasmine S. Bettina & Qiang Chen & Aaron L. Goldman & Michael D. Gregory & Kira Griffiths & Thom, 2024. "Dopamine signaling enriched striatal gene set predicts striatal dopamine synthesis and physiological activity in vivo," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0009348. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.