Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation
577—Molecular Mechanisms of Memory Reconsolidation and Retrieval
Tuesday, November 12, 2013, 8:00 am - 12:00 noon
577.17: Effects of dopamine D1 receptor antagonism on the reconsolidation of contextual fear memory
Location: Halls B-H
">*C. STEVENSON1, J. L. C. LEE2, J. P. VOIGT1, F. C. HEATH1; 1Univ. Nottingham, Loughborough, United Kingdom; 2Univ. of Birmingham, Birmingham, United Kingdom
Abstract Body: Once encoded, memories can be updated through reconsolidation to maintain their relevance. This process entails retrieval-induced destablization of the memory followed by its restabilization. Memory updating is thought to involve prediction error signalling which, in turn, is associated with dopamine cell activity. However, the role of dopamine transmission in memory reconsolidation remains unclear. Here we investigated the effects of the D1 receptor antagonist SCH 23390 on the reconsolidation of contextual fear memory in rats. In Experiment 1, animals were subjected to contextual fear conditioning (4 shocks). The next day SCH 23390 was given systemically 30 min before or immediately after brief (2 min) memory reactivation. Post-reactivation long-term memory was tested one day (PR-LTM1) and again one week (PR-LTM2) later. Freezing behaviour during memory testing served as a measure of contextual fear. We found no effects of SCH 23390 given before or after memory reactivation on freezing during reactivation, PR-LTM1 or PR-LTM2 testing. These results suggest that D1 receptor signalling is not involved in the retrieval or post-reactivation restabilization of contextual fear memory. It is also possible that the lack of effect of SCH 23990 was related to potential boundary conditions associated with our behavioural parameters; using weaker conditioning or longer reactivation may have allowed SCH 23390 to affect reconsolidation. Thus, in Experiment 2, we examined the effects of the NMDA receptor antagonist MK-801 on the retrieval and post-reactivation restabilization of contextual fear memory with the same behavioural parameters used in Experiment 1. Rats were conditioned and the next day MK-801 was given systemically 30 min before memory reactivation. We found that MK-801 decreased freezing during reactivation, PR-LTM1 and PR-LTM2 testing. These results confirm previous findings showing that NMDA receptor antagonism disrupts the post-reactivation restabilization of contextual fear memory. They also suggest that the lack of effect of SCH 23390 shown in Experiment 1 was unlikely due to any boundary conditions related to the behavioural parameters used. Ongoing experiments are examining if SCH 23390 given before reactivation prevents the disruptive effects of MK-801 on post-reactivation restabilization; this would suggest that D1 receptor signalling plays a role in memory destabilization, in keeping with emerging evidence linking this reconsolidation process with prediction error signalling, dopamine transmission and memory updating.
Lay Language Summary: Remembering events can trigger memory traces to become physically unstable before they are made stable again through a process called reconsolidation. Our research suggests that the brain chemical dopamine is not involved in making a memory trace stable again after remembering. Our ongoing work is investigating if dopamine is involved in first making the memory trace unstable. Reconsolidation allows memories to be updated to stay relevant by incorporating new learning into the original memory. Understanding how this process works is important as learning from experience and adapting to change are essential for survival. It might also be possible to target reconsolidation to treat psychiatric disease in the future. Anxiety disorders (e.g. post-traumatic stress) and addiction are associated with abnormally strong emotional memories. One possible treatment strategy is to have patients remember their traumatic or addictive drug-related experiences while under the influence of a drug that enhances the memory trace becoming unstable or disrupts it from later becoming stable again. This could effectively erase unwanted memories. To develop this type of treatment approach we first need to understand more about the reconsolidation process. Dopamine is crucial for new learning, so it might also be involved in memory updating through reconsolidation. To test this, we investigated if a drug that blocks the action of dopamine interferes with a memory trace becoming stable again after remembering an emotional event. Rats were trained to fear a new environment by giving them mild electric shocks in a chamber. The next day they were given the drug either before or after being returned to the chamber for a reminder session. The following day, the rats were tested to see if they still showed fear in the chamber to determine if the drug given the day before altered the memory trace. We found no effects of the drug, given before or after the reminder session, on fear behaviour at test the next day. This suggests that dopamine might not be involved in making memory traces more stable after remembering. However, studies show that other drugs which disrupt this process only have their effects under certain conditions. To address this, we tested a second drug that blocks the action of glutamate, a brain chemical important for reconsolidation. We found that this second drug, when given before the reminder session, reduced fear behaviour at test. This shows that blocking glutamate disrupted the memory trace from becoming stable again after remembering, as others have shown. It also shows that we can disrupt this process with the procedures used in our research. Our ongoing work is investigating if dopamine is involved in first making the fear memory trace unstable by remembering during the reminder session. To test this, we are investigating the effects of blocking dopamine before the reminder session, in combination with blocking glutamate after the reminder session, on fear behaviour at test. Dopamine blockade alone should have no effect on fear behaviour during the testing session as this would prevent the memory trace from becoming unstable, leaving it intact. Crucially, protecting the memory trace by blocking dopamine before remembering should keep it from being disrupted by later glutamate blockade. This should also result in no effect on fear behaviour at test. Our preliminary data suggest that this is the case. Understanding how dopamine makes memory traces unstable through remembering could lead to dopamine boosting drugs, which are already in use for treating Parkinson’s disease and attention deficit hyperactivity disorder, being used to treat anxiety disorders and addiction in the future.
Neuroscience 2013 (43rd annual meeting of the Society for Neuroscience)Exit