Dopamine modulates episodic memory persistence in old age.
Activation of the hippocampus is required to encode memories for new events (or episodes). Observations from animal studies suggest that, for these memories to persist beyond 4-6 h, a release of dopamine generated by strong hippocampal activation is needed. This predicts that dopaminergic enhancement should improve human episodic memory persistence also for events encoded with weak hippocampal activation. Here, using pharmacological functional MRI (fMRI) in an elderly population in which there is a loss of dopamine neurons as part of normal aging, we show this very effect. The dopamine precursor levodopa led to a dose-dependent (inverted U-shape) persistent episodic memory benefit for images of scenes when tested after 6 h, independent of whether encoding-related hippocampal fMRI activity was weak or strong (U-shaped dose-response relationship). This lasting improvement even for weakly encoded events supports a role for dopamine in human episodic memory consolidation, albeit operating within a narrow dose range.
Institute of Cognitive Neuroscience, University College London, London, WC1N 3AR, United Kingdom. rumana.chowdhury@ucl.ac.uk
Rumana
R
Chowdhury
Marc
M
Guitart-Masip
Nico
N
Bunzeck
Raymond J
RJ
Dolan
Emrah
E
Düzel
D000368:Aged; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D015331:Cohort Studies; D018592:Cross-Over Studies; D004298:Dopamine / Q000502:physiology*; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D061212:Memory, Episodic; D010775:Photic Stimulation / Q000379:methods
D015259:Dopamine Agents; D007980:Levodopa; D004298:Dopamine