Optogenetic Destabilization of the Memory Trace in CA1: Insights into Reconsolidation and Retrieval Processes

Abstract

Reactivation of memory can cause instability necessitating the reconsolidation of the trace. This process can be blocked by amnestic treatments administered after memory reactivation resulting in subsequent memory deficits. While the basolateral amygdala (BLA) is known to be crucial for reconsolidation, evidence for a contribution of the hippocampal CA1 region has only started to accumulate. Moreover, the effect of a reconsolidation blockade in CA1 has only been evaluated behaviorally, and it is unknown whether this manipulation has a long-term effect on neuronal activity. We combined optogenetic and high-resolution molecular imaging techniques to inhibit cell firing in CA1 following the reactivation of a fear memory in mice, evaluated memory performance and imaged neuronal activity the next day upon reexposure to the conditioning context. Blocking memory reconsolidation led to severe memory impairments that were associated with reduced neuronal activity not only in CA1 but also in CA3 and the BLA. Thus, our results indicate that CA1 is necessary for reconsolidation and suggest the involvement of a CA3-CA1-BLA network in the retrieval of contextual fear memory. Further investigations of this network might contribute to the validation of new brain targets for the treatment of pathologies such as posttraumatic stress disorders.

Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long‐term maintenance during consolidation

“…Here, we shown a reduced susceptibility not only to fear extinction, but also to clonidine‐induced reconsolidation disruption, of a fear memory consolidated under NR inactivation. Considering that a successful memory destabilization upon retrieval and reactivation depends on the recruitment of most brain regions associated with its formation (Liu et al, ; de Oliveira Alvares et al, ; Piñeyro, Monti, Alfei, Bueno, & Urcelay, ; Lux, Masseck, Herlitze, & Sauvage, ), a potential explanation for these results could be an insufficient labilization of the memory due to a difference in the relative contribution of the brain regions involved in its consolidation and reactivation (Lee, Nader, & Schiller, ). In other words, the experimental intervention conducted here could have rendered a fear memory less congruent and, thus, less prone to destabilization, context‐dependent extinction (Bouton, ) and updating through reconsolidation (de Oliveira Alvares et al, ).…”

Regulation of the Expression of the Psychiatric Risk Gene <b><i>Cacna1c</i></b> during Associative Learning

“…This regulation in CA1 may not be directly linked with novelty processing per se, a function co-ordinated by the DG and CA3 regions [38, 39], but with the role of the hippocampus in the formation and storage of the conjunctive representation of the context necessary for the consolidation and reconsolidation of CFC [40-42]. The regulation of Cacna1c expression in CA1 is therefore consistent with its role as a key region for the consolidation and reconsolidation of contextual fear (CS-US) memory [43-45]. The regulation of Cacna1c expression in both DG and CA1 after acquisition but not recall (CA1 only) is consistent with the differential contributions of these two hippocampal regions to CFM acquisition and retrieval [46].…”

Responsiveness of dentate neurons generated throughout adult life is associated with resilience to cognitive aging

“…These conclusions have been obtained using the hippocampal‐dependent version of the Morris water maze (measuring reference memory with variable starting points), one of the most widely used behavioral tests to study normal aging in rats; this task does not involve food restriction or the administration of shock to encourage participation of old animals and is very sensitive to the aging process (Kennard & Woodruff‐Pak, 2011; Lubec et al., 2019; Mota et al., 2019). Although inter‐individual differences in memory in aged rats have been demonstrated in other type of mazes (Barrett, Bennie, Trieu, Ping, & Tsafoulis, 2009; Temido‐Ferreira et al., 2018), in object location memory tasks (Lux, Masseck, Herlitze, & Sauvage, 2017), and in the hole‐board task (Lubec et al., 2019), we chose to use the water maze because it is the most widely used task to study the implication of adult‐born neurons in aged rats (our own work, (Bizon & Gallagher, 2003; Marrone, Ramirez‐Amaya, & Barnes, 2012)) whereas their role remains largely unexplored using the other tasks.…”