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. Projections from the locus coeruleus, an area typically defined by noradrenergic signalling, to the hippocampus drive novelty-based memory enhancement through possible co-release of dopamine. Memory retention can be enhanced when something novel or categorically relevant occurs shortly before or after the time of memory encoding, as in 'flashbulb memory'. Dopamine-based mechanisms originating in the ventral tegmental area have been implicated in the phenomenon. These authors suggest that projections from the locus coeruleus—typically defined by noradrenergic signalling—to the hippocampus drive this novelty-based memory enhancement through the possible local release of dopamine.

Locus coeruleus and dopaminergic consolidation of everyday memory