Erika Atucha, Vanja Vukojevic, Raquel V. Fornari, Giacomo Ronzoni, Philippe Demougin, Fabian Peter, Piray Atsak, Marcel W. Coolen, Andreas Papassotiropoulos, James L. McGaugh, Dominique J.-F. de Quervain, and Benno RoozendaalPNAS August 22, 2017 114 (34) 9176-9181; first published August 8, 2017 https://doi.org/10.1073/pnas.1710819114
- Contributed by James L. McGaugh, July 18, 2017 (sent for review June 15, 2017; reviewed by Ivan Izquierdo and Carmen Sandi)
Emotional arousal creates lasting and vivid memories. According to the systems consolidation theory, the hippocampus has a time-limited role in memory, and retrieval of remote memories mainly relies on neocortical networks. Here we show that this systems consolidation and associated change in memory specificity constitute a dynamically regulated process that can be modified by emotional arousal status. Norepinephrine administration into the basolateral amygdala after an episodic-like training experience maintained accuracy and hippocampus dependency of remote memory. This altered systems consolidation was paralleled by time-regulated epigenetically driven transcriptional changes of memory-related genes in the hippocampus and neocortex.
Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline- and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock–context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkmζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.