Dopamine Related Genes Differentially Affect Declarative Long-Term Memory in Healthy Humans

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.

Oligonol ameliorates liver function and brain function in the 5 × FAD mouse model: transcriptional and cellular analysis

“…The volcano graph demonstrates the distinguishing genes of the dopamine transporter Slc6a3 gene, related to neuropsychiatric diseases, 109,110 Tph2, related to serotonergic neuronal cell regulation, 111,112 and Gh, related to inflammation. 113 In addition, our transcriptome data showed 20 increased genes, including Cdh12, related to the upregulation of neurite growth; 114 Apold1, associated with angiogenesis and blood brain permeability; 115,116 Poc1a, related to the regulation of neuronal spindle function; 117 Kcnh7, associated with the downregulation of schizophrenia; 118 Atp2b, related to the protection of γ-aminobutyric acid (GABA)ergic neurons; 119 Cnr1, related to mood disorder and dopaminergic neurotransmission; 120,121 Camp4, related to the upregulation of memory formation improvement; 122 Dclk3, associated with neuroprotective function in the dentate gyrus in hippocampal formation and Huntington's disease; 123 Pde10a, related to regulation of the dopamine system in neurons; 124 Rgs4, associated with neurotransmitter transmission, psychiatric disorders such as depression and autism, and cognition; [125][126][127] Cdkl5, related to the downregulation of seizure and motor dysfunction; 128 Homer1, related to the downregulation of epilepsy, autism, addiction, schizophrenia, and depression; 128 Hivep2, related to the regulation of dopaminergic neurons; 129 and Syt1, related to the regulation of neurotransmitter release 130 in the 5 × FAD mouse hippocampus after oligonol treatment.…”

A computational model of current control mechanism for long‐term potentiation (LTP) in human episodic memory based on gene–gene interaction

“…Various forms and levels of episodic memory are formed due to these processes that are activated and established by intracellular, molecular, gene-level signalling cascades, various changes and expression of genes (Otmakhov et al, 2004;Sumi & Harada, 2023;Wang et al, 2006). These forms of episodic memory are sensory memory (immediate), working memory (lasting for seconds), short-term memory (lasting minutes), intermediate-term memory (lasting for hours) and longterm memory (lasting days to a lifetime) (Leukel et al, 2020;Tulving, 1972Tulving, , 1983Tulving, , 2002.…”