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Einar Örn Einarsson"Cellular and systems consolidation and reconsolidation of recent and remote contextual fear memory in the anterior cingulate cortex"

Abstract :

Memories undergo a prolonged period of reorganization in the brain after learning.
In tasks such as contextual fear conditioning, the hippocampus (HC) has been posited to play a time-limited role in mediating memory retrieval, being critical at more recent-time points (e.g. 1 day post-training), but not at remote ones (e.g. 30 days post-training), a process called systems consolidation. In contrast, the anterior cingulate cortex (ACC) has been found to be critical for retrieval of remote, but not recent memories.
In my doctoral dissertation work I assessed the involvement of the ACC in cellular consolidation and reconsolidation of recent and remote contextual fear memories, and systems reconsolidation following the retrieval of remote memories. First, we asked if the specific involvement of the ACC in mediating remote memory was also reflected in the participation of this structure in cellular reconsolidation of remote memory, but not cellular consolidation or reconsolidation of recent memory. Second, we asked whether retrieval of remote memory induces systems reconsolidation where a memory returns transiently from an ACC-dependent state to a dorsal HC-dependent one, and if such changes in functional requirements of the ACC and the dorsal HC were reflected by neural activity as indicated by c-Fos protein expression. Third, we tested whether more generalized contextual fear memory expression of remote memories was mediated by the ACC. We found that contextual fear memories undergo cellular consolidation in the ACC following training, and reconsolidation at 3 and 30 days post-training as indicated by sensitivity to local anisomycin infusion immediately following training / retrieval. Second, using two complementary approaches of pharmacological AMPAR inactivation and measurement of the activity-dependent gene c-Fos, we found that following the retrieval of an ACC-dependent remote memory, subsequent retrieval 6 hrs later can transiently be supported by either the ACC or the dHC, as inactivating either structure does not impair expression, but inactivating both does. This pattern is mirrored by elevated ACC c-Fos activity and renewed dorsal HC-CA1 c-Fos activity at the same time point. Third, contextual generalization of fear memory expression increases with time, coinciding with the increased involvement of the ACC in memory retrieval. However, following the retrieval of a remote memory, context discrimination is restored 24 hours later, but not at 6 or 48 hours. Moreover, inactivation of the ACC 6 hours after the reminder session restores context discrimination, suggesting that the dorsal HC is mediating the more discriminative memory expression. Together, these findings suggest that although the ACC is preferentially required for expressing remote generalized memories, it is involved in stabilizing the memory trace from its encoding, and for restabilization thereafter.

Selected publications

Einarsson E.Ö., Nader, K. (2010). Reconsolidation and reorganization of recent and remote contextual fear memory in the anterior cingulate cortex. Neuron, under review – resubmission pending.

Hardt, O., Einarsson, E.Ö., & Nader, K. (2010). Bridge over troubled water: reconsolidation as a link between cognitive and neuroscientific memory research traditions. Annual Review in Psychology, 61,

Cyril Herry pour une candidature de Post doc