Bertolino, Alessandro

Blasi, Giuseppe

Caforio, Grazia

D'Ambrosio, Enrico

Di Giorgio, Annabella

Fazio, Leonardo

Gelao, Barbara

Masellis, Rita

Popolizio, Teresa

Quarto, Tiziana

Rampino, Antonio

Sadee, Wolfgang

Selvaggi, Pierluigi

Smith, Ryan M.

Taurisano, Paolo

Tomasicchio, Aldo

PLoS ONE

PubMed

Helsingin yliopiston digitaalinen arkisto

DRD2/CHRNA5 Interaction on Prefrontal Biology and Physiology during Working Memory

Annabella Di Giorgio

Ryan M. Smith

Leonardo Fazio

Enrico D'Ambrosio

Barbara Gelao

Aldo Tomasicchio

Pierluigi Selvaggi

Paolo Taurisano

Tiziana Quarto

Rita Masellis

Antonio Rampino

Grazia Caforio

Teresa Popolizio

Giuseppe Blasi

Wolfgang Sadee

Alessandro Bertolino

Crossref

Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume.A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI.We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups.The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5

Ryan M Smith

Directory of Open Access Journals

DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory.

<div>BackgroundPrefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume.MethodsA large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI.ResultsWe found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups.ConclusionsThe present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5.</div

Annabella Di Giorgio (252876)

Ryan M. Smith (272322)

Leonardo Fazio (252859)

Enrico D'Ambrosio (562817)

Barbara Gelao (252868)

Aldo Tomasicchio (562818)

Pierluigi Selvaggi (562819)

Paolo Taurisano (252853)

Tiziana Quarto (562820)

Rita Masellis (562821)

Antonio Rampino (562822)

Grazia Caforio (252878)

Teresa Popolizio (252896)

Giuseppe Blasi (252857)

Wolfgang Sadee (179657)

Alessandro Bertolino (252850)

The Francis Crick Institute

DRD2/CHRNA5 Interaction on Prefrontal Biology and Physiology during Working Memory

Background: Prefrontal behavior and activity in humans are heritable. Studies in animals demonstrate an interaction between dopamine D2 receptors and nicotinic acetylcholine receptors on prefrontal behavior but evidence in humans is weak. Therefore, we hypothesize that genetic variation regulating dopamine D2 and nicotinic acetylcholine receptor signaling impact prefrontal cortex activity and related cognition. To test this hypothesis in humans, we explored the interaction between functional genetic variants in the D2 receptor gene (DRD2, rs1076560) and in the nicotinic receptor α5 gene (CHRNA5, rs16969968) on both dorsolateral prefrontal cortex mediated behavior and physiology during working memory and on prefrontal gray matter volume. Methods: A large sample of healthy subjects was compared for genotypic differences for DRD2 rs1076560 (G>T) and CHNRA5 rs16969968 (G>A) on prefrontal phenotypes, including cognitive performance at the N-Back task, prefrontal physiology with BOLD fMRI during performance of the 2-Back working memory task, and prefrontal morphometry with structural MRI. Results: We found that DRD2 rs1076560 and CHNRA5 rs16969968 interact to modulate cognitive function, prefrontal physiology during working memory, and prefrontal gray matter volume. More specifically, CHRNA5-AA/DRD2-GT subjects had greater behavioral performance, more efficient prefrontal cortex activity at 2Back working memory task, and greater prefrontal gray matter volume than the other genotype groups. Conclusions: The present data extend previous studies in animals and enhance our understanding of dopamine and acetylcholine signaling in the human prefrontal cortex, demonstrating interactions elicited by working memory that are modulated by genetic variants in DRD2 and CHRNA5. © 2014 Di Giorgio et al

Giorgio, Annabella Di

FAZIO, LEONARDO

D'AMBROSIO, ENRICO

GELAO, BARBARA

TOMASICCHIO, ALDO

SELVAGGI, PIERLUIGI

TAURISANO, PAOLO

QUARTO, TIZIANA

MASELLIS, Rita

RAMPINO, ANTONIO

CAFORIO, GRAZIA

BLASI, GIUSEPPE

BERTOLINO, Alessandro

Archivio istituzionale della ricerca - Università di Bari

English

DRD2/CHRNA5 interaction on prefrontal biology and physiology during working memory

Archivio Istituzionale della Ricerca- Università degli Studi di Foggia

http://dx.doi.org/10.1371/journal.pone.0095997

DRD2/CHRNA5 Interaction on Prefrontal Biology and Physiology during Working Memory

Abstract

Similar works

Full text

Available Versions

Helsingin yliopiston digitaalinen arkisto

Crossref

Directory of Open Access Journals

The Francis Crick Institute

Archivio istituzionale della ricerca - Università di Bari

Archivio Istituzionale della Ricerca- Università degli Studi di Foggia