Memory Reconsolidation and Extinction Have Distinct Temporal and Biochemical Signatures

Abstract

Memory retrieval is not a passive phenomenon. Instead, it triggers a number of processes that either reinforce or alter stored information. Retrieval is thought to activate a second memory consolidation cascade (reconsolidation) that requires protein synthesis. Here, we show that the temporal dynamics of memory reconsolidation are dependent on the strength and age of the memory, such that younger and weaker memories are more easily reconsolidated than older and stronger memories. We also report that reconsolidation and extinction, two opposing processes triggered by memory retrieval, have distinct biochemical signatures: pharmacological antagonism of either cannabinoid receptor 1 or L-type voltage-gated calcium channels blocks extinction but not reconsolidation. These studies demonstrate the dynamic nature of memory processing after retrieval and represent a first step toward a molecular dissection of underlying mechanisms.

Inhibition of Fatty-Acid Amide Hydrolase Accelerates Acquisition and Extinction Rates in a Spatial Memory Task

“…However this interpretation is somewhat limited by the fact that SR141716 given alone delayed extinction. As previously described in a similar water maze task (Varvel et al, 2005a) and in conditioned fear paradigms (Marsicano et al, 2002;Suzuki et al, 2004;Chhatwal et al, 2005), SR141716 robustly attenuated extinction in the present experiment. The effect of SR141716 presented here replicates our previously published report, with some minor procedural differences such as the weekly extinction trials (as opposed to bi-weekly trials) and the inclusion of the quadrant data.…”

“…These findings support the hypothesis that the endocannabinoid system plays an important role in modulating extinction learning (Marsicano et al, 2002;Suzuki et al, 2004;Varvel et al, 2005a). In contrast, a wide dose range of THC failed to have any significant effects on extinction.…”

“…For example, NMDA antagonists, voltage-gated calcium channel blockers, benzodiazepines, and dopaminergic modulators have all been reported to disrupt extinction, whereas facilitation of extinction has been observed with the partial NMDA agonist D-cycloserine, and the GABA A antagonist picrotoxin (Myers and Davis, 2002). Recently, both CB 1 receptor (À/À) mice and mice treated with the CB 1 antagonist SR141716 (rimonabant) displayed impaired extinction in conditioned fear tests (Marsicano et al, 2002;Suzuki et al, 2004), as well as in the Morris water maze (Varvel et al, 2005a). Taken together, the results of these studies support the hypothesis that the endocannabinoid system participates in processes underlying extinction learning.…”

Cannabidiol as a Potential Treatment for Anxiety Disorders

“…Briefly, fear memories, when reactivated by re-exposure (retrieval), enter into a labile state in which the memory trace may either be reconsolidated or extinguished [97], and this process may be pharmacologically modulated to achieve reconsolidation blockade or extinction. When administered immediately following retrieval, CBD prevented freezing to the conditioned context upon further re-exposure, and no reinstatement or spontaneous recovery was observed over 3 weeks, consistent with reconsolidation blockade rather than extinction [76].…”

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

“…Given the role of NMDARs in the induction of synaptic plasticity (Martin et al, 2000;Riedel et al, 2003), the most likely interpretation of these results is that the synaptic plasticity required for the acquisition of fear extinction was disrupted. However, two studies (Santini et al, 2001;Suzuki et al, 2004), using a different measure of fear (freezing rather than potentiated startle) and systemic infusions of the non-subunit selective NMDAR antagonist CPP ((7)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid), found that whereas the retention of extinction was impaired, there was no apparent impairment during the acquisition of extinction.…”