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A variable number of tandem repeats in the 3′‐untranslated region of the dopamine transporter modulates striatal function during working memory updating across the adult age span
Author(s) -
Sambataro Fabio,
Podell Jamie E.,
Murty Vishnu P.,
Das Saumitra,
Kolachana Bhaskar,
Goldberg Terry E.,
Weinberger Daniel R.,
Mattay Venkata S.
Publication year - 2015
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.12956
Subject(s) - dopamine transporter , striatum , dopamine , variable number tandem repeat , biology , neuroscience , tandem repeat , working memory , psychology , allele , dopaminergic , genetics , cognition , gene , genome
Dopamine modulation of striatal function is critical for executive functions such as working memory ( WM ) updating. The dopamine transporter ( DAT ) regulates striatal dopamine signaling via synaptic reuptake. A variable number of tandem repeats in the 3′‐untranslated region of SLC 6A3 ( DAT 1 ‐3′‐ UTR ‐ VNTR ) is associated with DAT expression, such that 9‐repeat allele carriers tend to express lower levels (associated with higher extracellular dopamine concentrations) than 10‐repeat homozygotes. Aging is also associated with decline of the dopamine system. The goal of the present study was to investigate the effects of aging and DAT 1 ‐3′‐ UTR ‐ VNTR on the neural activity and functional connectivity of the striatum during WM updating. Our results showed both an age‐related decrease in striatal activity and an effect of DAT 1 ‐3′‐ UTR ‐ VNTR . Ten‐repeat homozygotes showed reduced striatal activity and increased striatal–hippocampal connectivity during WM updating relative to the 9‐repeat carriers. There was no age by DAT 1 ‐3′‐ UTR ‐ VNTR interaction. These results suggest that, whereas striatal function during WM updating is modulated by both age and genetically determined DAT levels, the rate of the age‐related decline in striatal function is similar across both DAT 1 ‐3′‐ UTR ‐ VNTR genotype groups. They further suggest that, because of the baseline difference in striatal function based on DAT 1 ‐3′‐ UTR ‐ VNTR polymorphism, 10‐repeat homozygotes, who have lower levels of striatal function throughout the adult life span, may reach a threshold of decreased striatal function and manifest impairments in cognitive processes mediated by the striatum earlier in life than the 9‐repeat carriers. Our data suggest that age and DAT 1 ‐3′‐ UTR ‐ VNTR polymorphism independently modulate striatal function.