RESEARCH HIGHLIGHTS

Nature Reviews Neuroscience | AOP, published online 15 November 2012; doi:10.1038/nrn3385

L E A R N I N G A N D M E M O RY

Dopamine boosts ageing memories

augmentation Research in animal studies suggests
of dopaminergic that the formation of memories of
events (episodic memory) depends
signalling on the activation of hippocampal
in humans CA1 glutamatergic synapses, and that
enhances the for these memories to become long
lasting, dopamine is also required.
persistence
The relevance of these findings for
of episodic the formation of episodic memory
memory in humans is poorly understood, but
Chowdhury et al. now provide evi-
dence that augmentation of dopamin-
ergic signalling in humans enhances
memory follows similar principles,
artificially increasing dopamine in
the hippocampus should result
in strengthened synapses — and
episodic memory persistence — even
after weak hippocampal stimulation.
Loss of dopamine neurons —
and a decline in episodic memory
— are part of normal ageing. The
authors boosted dopaminergic
neurotransmission in a group of
elderly subjects by giving them the
dopamine precursor levodopa and
was also enhanced. It might be possi-
ble to harness this effect of dopamine
on memory consolidation therapeu-
tically to compensate for age-related
memory decline.
Sian Lewis
ORIGINAL RESEARCH PAPER Chowdhury, R.
et al. Dopamine modulates episodic memory
persistence in old age. J. Neurosci. 32,
14193−14204 (2012)
FURTHER READING Lisman, J., Grace, A. A. &
Duzel, E. A neoHebbian framework for episodic
memory; role of dopamine-dependent late LTP.
Trends Neurosci. 34, 536−547 (2011)

the persistence of episodic memory.
Electrophysiological studies in
rodents have indicated that the initial
stages of episodic memory forma-
tion involve changes in the synaptic
strength of excitatory CA1 synapses
that follow Hebbian principles — they
require simultaneous presynaptic
glutamate release and postsynaptic
depolarization. For these changes in
synaptic strength to persist beyond
4−6 hours, protein synthesis that
depends on hippocampal dopamine
release is necessary. Weakly encoded
stimuli that are not sufficient to
evoke hippocampal dopamine release
are not retained beyond 6 hours.
then tested how well they could
remember visual scenes 6 hours
or more after they were presented.
This time point is associated with
post-encoding, protein synthesis-
dependent memory consolidation.
The authors used pharmacological
functional MRI to determine levels
of activation (encoding) within the
hippocampus. Pretreatment with
levodopa enhanced recall, with the
dose−response curve following an
inverted U-shape. Recollection at
earlier time points was unaffected
by levodopa administration when
compared with placebo. Interestingly,
recall of weakly encoded events (that
GETTY

The authors reasoned that if human had a weak functional MRI signal)

NATURE REVIEWS | NEUROSCIENCE VOLUME 13 | DECEMBER 2012

© 2012 Macmillan Publishers Limited. All rights reserved