D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans

Leonardo Fazio, Giuseppe Blasi, Paolo Taurisano, Apostolos Papazacharias, Raffaella Romano, Barbara Gelao, Gianluca Ursini, Tiziana Quarto, Luciana Lo Bianco, Annabella Di Giorgio, Marina Mancini, Teresa Popolizio, Giuseppe Rubini, Alessandro Bertolino

Research output: Contribution to journalArticle

Abstract

Objective: Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [123I] FP-CIT SPECT. Methods: Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [123I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. Results: Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. Interpretation: The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease.

Original languageEnglish
Pages (from-to)2915-2921
Number of pages7
JournalNeuroImage
Volume54
Issue number4
DOIs
Publication statusPublished - Feb 14 2011

Keywords

  • [I] FP-CIT SPECT
  • Dopamine D2 Receptor Polymorphism
  • FMRI
  • Imaging genetics
  • Motor brain activity
  • Multimodal

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Neurology

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  • Cite this

    Fazio, L., Blasi, G., Taurisano, P., Papazacharias, A., Romano, R., Gelao, B., Ursini, G., Quarto, T., Lo Bianco, L., Di Giorgio, A., Mancini, M., Popolizio, T., Rubini, G., & Bertolino, A. (2011). D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans. NeuroImage, 54(4), 2915-2921. https://doi.org/10.1016/j.neuroimage.2010.11.034