Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance

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

Research output: Contribution to journalArticle

65 Citations (Scopus)

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.

Original languageEnglish
Article numbere9348
JournalPLoS One
Volume5
Issue number2
DOIs
Publication statusPublished - Feb 22 2010

Fingerprint

Corpus Striatum
Short-Term Memory
dopamine
Data storage equipment
receptors
Dopamine Plasma Membrane Transport Proteins
Neurotransmitter Receptor
transporters
Dopamine
Prefrontal Cortex
Single Nucleotide Polymorphism
Magnetic Resonance Imaging
Factor analysis
Neurons
Dopamine D2 Receptors
Memory Disorders
Protein Isoforms
Genes
neurons
Single-Photon Emission-Computed Tomography

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bertolino, A., Taurisano, P., Pisciotta, N. M., Blasi, G., Fazio, L., Romano, R., ... Rubini, G. (2010). Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance. PLoS One, 5(2), [e9348]. https://doi.org/10.1371/journal.pone.0009348

Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance. / Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe.

In: PLoS One, Vol. 5, No. 2, e9348, 22.02.2010.

Research output: Contribution to journalArticle

Bertolino, A, Taurisano, P, Pisciotta, NM, Blasi, G, Fazio, L, Romano, R, Gelao, B, Lo Bianco, L, Lozupone, M, Di Giorgio, A, Caforio, G, Sambataro, F, Niccoli-Asabella, A, Papp, A, Ursini, G, Sinibaldi, L, Popolizio, T, Sadee, W & Rubini, G 2010, 'Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance', PLoS One, vol. 5, no. 2, e9348. https://doi.org/10.1371/journal.pone.0009348
Bertolino, Alessandro ; Taurisano, Paolo ; Pisciotta, Nicola Marco ; Blasi, Giuseppe ; Fazio, Leonardo ; Romano, Raffaella ; Gelao, Barbara ; Lo Bianco, Luciana ; Lozupone, Madia ; Di Giorgio, Annabella ; Caforio, Grazia ; Sambataro, Fabio ; Niccoli-Asabella, Artor ; Papp, Audrey ; Ursini, Gianluca ; Sinibaldi, Lorenzo ; Popolizio, Teresa ; Sadee, Wolfgang ; Rubini, Giuseppe. / Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance. In: PLoS One. 2010 ; Vol. 5, No. 2.
@article{3c64691747a14b0fb2248369d6072a3a,
title = "Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance",
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.",
author = "Alessandro Bertolino and Paolo Taurisano and Pisciotta, {Nicola Marco} and Giuseppe Blasi and Leonardo Fazio and Raffaella Romano and Barbara Gelao and {Lo Bianco}, Luciana and Madia Lozupone and {Di Giorgio}, Annabella and Grazia Caforio and Fabio Sambataro and Artor Niccoli-Asabella and Audrey Papp and Gianluca Ursini and Lorenzo Sinibaldi and Teresa Popolizio and Wolfgang Sadee and Giuseppe Rubini",
year = "2010",
month = "2",
day = "22",
doi = "10.1371/journal.pone.0009348",
language = "English",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance

AU - Bertolino, Alessandro

AU - Taurisano, Paolo

AU - Pisciotta, Nicola Marco

AU - Blasi, Giuseppe

AU - Fazio, Leonardo

AU - Romano, Raffaella

AU - Gelao, Barbara

AU - Lo Bianco, Luciana

AU - Lozupone, Madia

AU - Di Giorgio, Annabella

AU - Caforio, Grazia

AU - Sambataro, Fabio

AU - Niccoli-Asabella, Artor

AU - Papp, Audrey

AU - Ursini, Gianluca

AU - Sinibaldi, Lorenzo

AU - Popolizio, Teresa

AU - Sadee, Wolfgang

AU - Rubini, Giuseppe

PY - 2010/2/22

Y1 - 2010/2/22

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77949606061&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949606061&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0009348

DO - 10.1371/journal.pone.0009348

M3 - Article

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e9348

ER -