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Nature. 2016 Sep 15;537(7620):357-362. doi: 10.1038/nature19325. Epub 2016 Sep 7.

Locus coeruleus and dopaminergic consolidation of everyday memory.

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Centre for Cognitive and Neural Systems, Edinburgh Neuroscience, The University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.
University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638, Japan.
Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, Nijmegen, 6525 EZ, The Netherlands.
Departments of Psychiatry and Behavioral Sciences and of Bioengineering, Stanford University, Stanford, California 94305, USA.
International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, 305-8575, Japan.
Instituto de Neurociencias, CSIC-UMH, Alicante, 03550, Spain.


The retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine-hydroxylase-expressing (TH+) neurons in the ventral tegmental area. Here we report that neuronal firing in the locus coeruleus is especially sensitive to environmental novelty, locus coeruleus TH+ neurons project more profusely than ventral tegmental area TH+ neurons to the hippocampus, optogenetic activation of locus coeruleus TH+ neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by ventral tegmental area inactivation. Surprisingly, two effects of locus coeruleus TH+ photoactivation are sensitive to hippocampal D1/D5 receptor blockade and resistant to adrenoceptor blockade: memory enhancement and long-lasting potentiation of synaptic transmission in CA1 ex vivo. Thus, locus coeruleus TH+ neurons can mediate post-encoding memory enhancement in a manner consistent with possible co-release of dopamine in the hippocampus.

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Conflict of interest statement

The authors declare no competing financial interests. Readers are welcome to comment on the online version of the paper.

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