Boundary Conditions Of Reconsolidation Research Articles

Over the Edge: Extending the duration of a reconsolidation intervention for spider fear

Pharmacologically disrupting fear memory reconsolidation dramatically reduces fear behaviour. For example, 2–3 min of tarantula exposure followed by 40 mg of propranolol HCl (i.e., a reconsolidation intervention) abruptly decreased spider avoidance, an effect that persisted one year later. However, the success of reconsolidation interventions is not guaranteed: Pavlovian fear-conditioning research shows that the window to target memory reconsolidation is small and easy to miss. If exposure is too long to trigger reconsolidation, but too short for extinction learning, an inactive transitional limbo state occurs, rendering the fear memory unchanged and insensitive to amnesic agents. In this pre-registered study, we aimed to find this behaviourally-controlled boundary condition. Spider-fearful participants underwent a ~3 min (n = 23) or ~14 min (n = 20) exposure to a tarantula, intended to trigger reconsolidation or the limbo state respectively, followed by 40 mg of propranolol. We expected greater spider fear reduction after 3 than 14 min of exposure. Unexpectedly, there were no group differences on any outcome measures. In both groups, Bayesian analysis revealed a marked reduction in fear behaviour towards a generalisation stimulus (a house spider) accompanied by lower self-reported distress, with a sharp decline in spider fear scores two days after treatment that persisted one year later. Possible explanations include that the boundary conditions of reconsolidation are wider in older and stronger memories than experimentally-induced fears, or that alternative processes caused the treatment effects. Although the mechanism is unclear, these results carry a tentative promising message for the potential of brief reconsolidation-targeting interventions to mitigate irrational fears.

A Model of Synaptic Reconsolidation.

Reconsolidation of memories has mostly been studied at the behavioral and molecular level. Here, we put forward a simple extension of existing computational models of synaptic consolidation to capture hippocampal slice experiments that have been interpreted as reconsolidation at the synaptic level. The model implements reconsolidation through stabilization of consolidated synapses by stabilizing entities combined with an activity-dependent reservoir of stabilizing entities that are immune to protein synthesis inhibition (PSI). We derive a reduced version of our model to explore the conditions under which synaptic reconsolidation does or does not occur, often referred to as the boundary conditions of reconsolidation. We find that our computational model of synaptic reconsolidation displays complex boundary conditions. Our results suggest that a limited resource of hypothetical stabilizing molecules or complexes, which may be implemented by protein phosphorylation or different receptor subtypes, can underlie the phenomenon of synaptic reconsolidation.

State-dependent effect of dopamine D1/D5 receptors inactivation on memory destabilization and reconsolidation

Object recognition memories (ORM) can incorporate new information upon reactivation. This update initially involves destabilization of the original memory, which is followed by restabilization of the upgraded engram through a reconsolidation process that requires gene expression and protein synthesis in the hippocampus. We found that when given in dorsal CA1 either immediately after training or 15min before ORM reactivation in the presence of a novel object, the dopamine D1/D5 receptor antagonist SCH23390 did not affect ORM consolidation, expression or retention but impeded the amnesia caused by the post-retrieval administration of the mRNA synthesis inhibitor α-amanitin or the protein synthesis blocker anisomycin. This anti-amnesic effect was not observed when SCH23390 was given immediately after training and again 15min before memory reactivation. Our results demonstrate that hippocampal D1/D5 receptors are not needed for formation, retrieval or post-retrieval restabilization of the ORM trace but are essential for its destabilization when reactivation occurs together with the incorporation of new information into the original memory. Importantly, they also suggest that reenactment of the animal's post-learning neurochemical milieu at the moment of memory reactivation can be a boundary condition for reconsolidation.

One retrieval trial induces reconsolidation in an appetitive learning paradigm in honeybees ( Apis mellifera)

Combining memory retrieval with the application of a protein synthesis-inhibitor leads to an amnestic effect that is referred to as the reconsolidation phenomenon. Several behavioural studies demonstrate that only a few or weak retrieval trials (that do not result in significant extinction) lead to this phenomenon. In contrast, many trials (that result in significant extinction) combined with a protein synthesis inhibitor result in an inhibition of the extinction memory. Based on these findings it was suggested that extinction is the boundary condition for reconsolidation: when extinction is induced the consolidation of the extinction memory is the dominant process. Recently we were not able to confirm this hypothesis in the honeybee ( Apis mellifera): We did not find the reconsolidation phenomenon after one retrieval trial, but demonstrated reconsolidation after five retrieval trials that led to extinction. To exclude that this observation resembles a special case in insects we here wanted to know if one retrieval trial induces reconsolidation as it has been demonstrated before in many other species. To do so we used experimental parameters that had been used before to demonstrate consolidation in the honeybee with the exception that this time the protein synthesis-inhibitor was applied 1 h after one memory retrieval instead after acquisition. We thereby demonstrate the reconsolidation phenomenon after one retrieval trial but only when using the doubled dose of protein synthesis-inhibitor that has been used to inhibit consolidation.