Abstract
In humans, monetary reward can promote behavioral performance including response times, accuracy, and subsequent recognition memory. Recent studies have shown that the dopaminergic system plays an essential role here, but the link to interindividual differences remains unclear. To further investigate this issue, we focused on previously described polymorphisms of genes affecting dopaminergic neurotransmission: DAT1 40 base pair (bp), DAT1 30 bp, DRD4 48 bp, and cannabinoid receptor type 1 (CNR1). Specifically, 669 healthy humans participated in a delayed recognition memory paradigm on two consecutive days. On the first day, male vs. female faces served as cues predicting an immediate monetary reward upon correct button presses. Subsequently, participants performed a remember/know recognition memory task on the same day and 1 day later. As predicted, reward increased accuracy and accelerated response times, which were modulated by DAT 30 bp. However, reward did not promote subsequent recognition memory performance and there was no interaction with any genotype tested here. Importantly, there were differential effects of genotype on declarative long-term memory independent of reward: (a) DAT1 40 bp was linked to the quality of memory with a more pronounced difference between recollection and familiarity in the heterozygous and homozygous 10-R as compared to homozygous 9-R; (b) DAT1 30 bp was linked to memory decay, which was most pronounced in homozygous 4-R; (c) DRD4 48 bp was linked to overall recognition memory with higher performance in the short allele group; and (d) CNR1 was linked to overall memory with reduced performance in the homozygous short group. These findings give new insights into how polymorphisms, which are related to dopaminergic neuromodulation, differentially affect long-term recognition memory performance.
Highlights
The dopaminergic system serves several, yet interconnected, functions
It revealed for DAT1 40 bp: 10-R 75.4%, 9-R 24.6%, Hardy–Weinberg equilibrium (HWE) χ 2 = 0.079, p = 0.78; for DAT 30 bp: 5-R 78.8%, 4-R 21.2%, HWE χ 2 = 0.012, p = 0.91; DA receptor D4 (DRD4) 48 bp: 7 R 18%, < 7 R 82%, HWE χ 2 = 0.0007, p = 0.97; and cannabinoid receptor type 1 (CNR1) bp: >12-R 67.8%, ≤ 12-R 32.2%, HWE χ 2 = 0.008, p = 0.93
While only one genotype polymorphism, namely DAT 30 bp, could be linked to reward dependent response times during encoding, reward had no impact on declarative long-term recognition memory and there was no interaction with any of the genotypes tested here
Summary
A functional loop between the medial temporal lobe and midbrain dopamine (DA) neurons drives the encoding of novel information into long-term memory (Lisman and Grace, 2005; Bunzeck and Düzel, 2006; Düzel et al, 2009; Bunzeck et al, 2014). DA neurons are known to be critical for reward processing (Schultz et al, 1997; Fiorillo et al, 2003; Tobler et al, 2005). Evidence for a link between reward processing and invigoration of behavior through dopaminergic neuromodulation comes from computational models and empirical studies in animals and humans (Niv et al, 2007; Guitart-Masip et al, 2011; Dayan, 2012; Beierholm et al, 2013; Steiger and Bunzeck, 2017). Specific genes that affect dopaminergic neuromodulation have been identified; yet the link between genetic polymorphisms and rewarddependent long-term memory remains less clear
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