Cited by 214Neurotransmitter Receptor Influence on BehaviorMemory and Neural MechanismsMemory Processes and Influences

The dopaminergic midbrain participates in human episodic memory formation: evidence from genetic imaging

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Schott, Björn H., Seidenbecher, Constanze I., Fenker, Daniela B., Lauer, Corinna J., Bunzeck, Nico, Bernstein, Hans-Gert, Tischmeyer, Wolfgang, Gundelfinger, Eckart D. +2 more·2006·The Journal of Neuroscience

Abstract

Recent data from animal studies raise the possibility that dopaminergic neuromodulation promotes the encoding of novel stimuli. We investigated a possible role for the dopaminergic midbrain in human episodic memory by measuring how polymorphisms in dopamine clearance pathways affect encoding-related brain activity (functional magnetic resonance imaging) in an episodic memory task. In 51 young, healthy adults, successful episodic encoding was associated with activation of the substantia nigra. This midbrain activation was modulated by a functional variable number of tandem repeat (VNTR) polymorphism in the dopamine transporter (DAT1) gene. Despite no differences in memory performance between genotype groups, carriers of the (low expressing) 9-repeat allele of the DAT1 VNTR showed relatively higher midbrain activation when compared with subjects homozygous for the 10-repeat allele, who express DAT1 at higher levels. The catechol-O-methyl transferase (COMT) Val108/158Met polymorphism, which is known to modulate enzyme activity, affected encoding-related activity in the right prefrontal cortex (PFC) and in occipital brain regions but not in the midbrain. Moreover, subjects homozygous for the (low activity) Met allele showed stronger functional coupling between the PFC and the hippocampus during encoding. Our finding that genetic variations in the dopamine clearance pathways affect encoding-related activation patterns in midbrain and PFC provides strong support for a role of dopaminergic neuromodulation in human episodic memory formation. It also supports the hypothesis of anatomically and functionally distinct roles for DAT1 and COMT in dopamine metabolism, with DAT1 modulating rapid, phasic midbrain activity and COMT being particularly involved in prefrontal dopamine clearance.

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Crossref · 10.1523/jneurosci.3463-05.2006

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Authors
Schott, B. H., Seidenbecher, C. I., Fenker, D. B., Lauer, C. J., Bunzeck, N., Bernstein, H.-G., Tischmeyer, W., Gundelfinger, E. D., Heinze, H.-J., & Düzel, E.
Affiliations
University Hospital Magdeburg (DE)
Venue
The Journal of Neuroscience
Published
2006-02-01
Volume
26
Issue
5
Pages
1407-1417
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1976031744
Cited by
214
References
65
Citations by year
2025: 1 · 2024: 3 · 2023: 7 · 2022: 3 · 2021: 3 · 2020: 10 · 2019: 6 · 2018: 3 · 2017: 11 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 20 · 2012: 18
FWCI
8.46
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Helmholtz-Gemeinschaft
  • Deutsche Forschungsgemeinschaft
  • Studienstiftung des Deutschen Volkes
  • Leibniz-Gemeinschaft
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
Keywords
dopaminergic midbrain, episodic memory encoding, substantia nigra, dopamine transporter gene, catechol-O-methyltransferase, COMT Val158Met polymorphism, prefrontal cortex, hippocampus, dopamine clearance, neuromodulation
MeSH terms
Adolescent, Adult, Behavior, Brain, Catechol O-Methyltransferase, Dopamine, Female, Genotype, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory, Mesencephalon, Polymorphism, Genetic, Mental Recall, Prefrontal Cortex, Tandem Repeat Sequences, Dopamine Plasma Membrane Transport Proteins

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