Under the curve: Critical issues for elucidating D1 receptor function in working memory

Williams, Graham V.; Castner, Stacy A.

doi:10.1016/j.neuroscience.2005.09.028

Cited by 289 publications

(226 citation statements)

References 163 publications

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“…9,53,54 Further studies systematically involving such interactions are needed to obtain a clearer overview of the dopaminergic pathway. At the same time, denser SNP coverage of the area under study is needed in genes like DRD2 to reveal the true functional variants, which while tagged, are still undiscovered.…”

Section: Discussionmentioning

confidence: 99%

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning

et al. 2008

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The COMT Val 108/158 Met polymorphism has been extensively studied in relation to individual differences in working memory (WM) performance. The present study tested the association of the COMT Val 108/158 Met polymorphism with WM performance in two independent family-based Dutch samples: 371 children (mean age 12.4 years) and 391 adults (mean age 36.2 years). A significant association was found between the COMT polymorphism and WM scores in the combined adult and young cohorts. The association reflected positive heterosis such that the Met/Met and Val/Val homozygotes did not perform as well as the Met/Val heterozygotes on the WM tasks. A secondary analysis was conducted in which a DRD2-tagging SNP (rs2075654) was tested for an interactive effect with the COMT polymorphism on WM performance. A significant interactive effect of the DRD2 and COMT genes was found such that heterosis was present only in the DRD2 genotype that has been linked to lower receptor density. Our results support previous findings that WM performance needs an optimal level of dopamine signaling within the PFC. This optimum level depends on enzymatic activity controlling dopamine level as well as dopamine receptor sensitivity, both of which may differ as a function of age and genotype. We conclude that the effects of a single polymorphism in a dopaminergic gene on a well-defined cognitive trait may easily remain hidden if the interaction with age and other genes in the pathway are not taken into account.

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Section: Discussionmentioning

confidence: 99%

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning

et al. 2008

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“…The importance of the balance in D1 signalling in the brain has been highlighted by the demonstration that excessive as well as insufficient D1 receptor stimulation impairs prefrontal cognitive function (Arnsten and Li, 2005b;Williams and Castner, 2006). ADHD is a complex disorder that occurs across the developmental spectrum, with the course of the illness changing over time.…”

Section: Discussionmentioning

confidence: 99%

Investigation of the G protein subunit Gαolf gene (GNAL) in attention deficit/hyperactivity disorder

Laurin

Ickowicz

Pathare

et al. 2008

Journal of Psychiatric Research

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The dopamine system plays an important role in the regulation of attention and motor behavior, subsequently, several dopamine-related genes have been associated with Attention Deficit/ Hyperactivity Disorder (ADHD). Among them are the dopamine receptors D1 and D5 that mediate adenylyl cyclase activation through coupling with G s -like proteins. We thus hypothesized that the G s -like subunit Gα olf , expressed in D1-rich areas of the brain, contributes to the genetic susceptibility of ADHD. To evaluate the involvement of the Gα olf gene, GNAL, in ADHD, we examined the inheritance pattern of 12 GNAL polymorphisms in 258 nuclear families ascertained through a proband with ADHD (311 affected children) using the transmission/disequilibrium test (TDT). Categorical analysis of individual marker alleles demonstrated biased transmission of one polymorphism in GNAL intron 3 (rs2161961; P = 0.011). We also observed significant relationships between rs2161961 and dimensional symptoms of inattention and hyperactivity/ impulsivity (P = 0.003 and P = 0.008). In addition, because of recent evidence of imprinting at the GNAL locus, secondary analyses were split into maternal and paternal transmissions to assess a contribution of parental effects. We found evidence of strong maternal effect, with preferential transmission of maternal alleles for rs2161961A (P = 0.005) and rs8098539A (P = 0.035). These preliminary findings suggest a possible contribution of GNAL in the susceptibility to ADHD, with possible involvement of parent-of-origin effects.

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“…Dopamine modulates delay activity in the prefrontal cortex (Williams and Goldman-Rakic, 1995;Williams and Castner, 2006). Mesencephalic potentially dopaminergic neurons can show sustained activity that varies according to uncertainty of obtaining a particular reward (Fiorillo et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Dorsolateral Prefrontal Delay Activity during Self-Organized Behavior

Procyk¹,

Goldman‐Rakic²

2006

J. Neurosci.

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The regulation of cognitive activity relies on the flexibility of prefrontal cortex functions. To study this mechanism we compared monkey dorsolateral prefrontal activity in two different spatial cognitive tasks: a delayed response task and a self-organized problem-solving task. The latter included two periods, a search by trial and error for a correct response, and a repetition of the response once discovered. We show that (1) delay activity involved in the delayed task also participates in self-generated responses during the problem-solving task and keeps the same location preference, and (2) the amplitude of firing and the strength of spatial selectivity vary with task requirement, even within search periods while approaching the correct response. This variation is dissociated from pure reward probability, but may have a link with uncertainty because the selectivity dropped when reward predictability was maximal. Overall, we show that spatially tuned delay activity of prefrontal neurons reflects the varying level of engagement in control between different spatial cognitive tasks and during self-organized behavior.

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Under the curve: Critical issues for elucidating D1 receptor function in working memory

Cited by 289 publications

References 163 publications

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning

Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene–gene interaction on working memory functioning

Investigation of the G protein subunit Gαolf gene (GNAL) in attention deficit/hyperactivity disorder

Modulation of Dorsolateral Prefrontal Delay Activity during Self-Organized Behavior

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