Mismatch between what is expected and what actually occurs triggers memory reconsolidation or extinction

Abstract

In previous experiments on contextual memory, we proposed that the unreinforced re-exposure to the learning context (conditioned stimulus, CS) acts as a switch guiding the memory course toward reconsolidation or extinction, depending on reminder duration. This proposal implies that the system computes the total exposure time to the context, from CS onset to CS offset, and therefore, that the reminder presentation must be terminated for the switching mechanism to become operative. Here we investigated to what extent this requirement is necessary, and we explored the relation between diverse phases in the reconsolidation and extinction processes. We used the contextual memory model of the crab Chasmagnathus which involves an association between the learning context (CS) and a visual danger stimulus (unconditioned stimulus, US). Administration of cycloheximide was used to test the lability state of memory at different time points. The results show that two factors, no-reinforcement during the reminder (i.e., CS re-exposure) and CS offset are the necessary conditions for both processes to occur. Regardless of the reminder duration, memory retrieved by unreinforced CS re-exposure emerges intact and consolidated when tested before CS offset, suggesting that neither reconsolidation nor extinction is concomitant with CS re-exposure. Either process could only be triggered once the definitive mismatch between CS and US is confirmed by CS termination without the expected reinforcement.

Figures

Figure 1

Reconsolidation is triggered after completion of short unreinforced context re-exposure. Experimental protocols and results. Day 1 (Training session): (A,B,C) Trained (TR) groups received 15 trials of the visual danger stimulus (VDS), intertrial interval: 3 min; control (CT) groups remained in the context for the entire session (45 min). Day 2 (Treatment session): (A) No VDS during context re-exposure; saline (SAL) injection to one-half of the CT-TR groups and cycloheximide (CHX) to the other half, given 2 h after re-exposure. (B) As in A but VDS during re-exposure. (C) As in B but SAL or CHX injections immediately after re-exposure. Day 3 (Test session): (A,B,C) One test trial. Open boxes represent context exposure; a set of several black bars inside the box represents 15 VDS presentations; only one black bar indicates one VDS during the last minute of exposure; a black arrow for saline (SAL) or cycloheximide (CHX) injection; numbers on the boxes indicate duration of the context exposure; numbers in brackets indicate time interval in hours. VDS trial (results) on Day 2 and 3: graph ordinates: mean response to VDS presentation ± SEM in arbitrary units; white bars for CT and TR groups, both SAL-injected; gray bars for CT and TR groups, both CHX-injected. **, P < 0.01.

Figure 2

Double context re-exposure. Experimental protocol and results. Day 1 (Training session) and Day 3 (Test session) as in Figure 1. Day 2 (Treatment session): Animals twice reexposed for 5 min: first time without VDS and second time, 4 h later, with VDS presentation. Once removed from container for the second time, animals were SAL- or CHX-injected. Symbols and VDS trial (results) on Days 2 and 3 as in Figure 1.

Figure 3

Extinction is triggered after completion of long unreinforced context re-exposure. Experimental protocols and results. Day 1 (Training session) and Day 3 (Test session): (A,B,C) As in Figure 1. Day 2 (Treatment session): (A,B) As in Figure 1. (C) Half of the CT-TR groups follow the interrupted (IN) protocol: context re-exposed for 2 h, then removed, and 4 h later replaced in the context for 5 min with VDS at last minute; and the other half, the uninterrupted (UN) protocol: 6 h of re-exposure with VDS at last minute. Symbols as in Figure 1. VDS trial (results) on Days 2 and 3: Ordinates: mean response to VDS presentation ± SEM in arbitrary units; striped white bars represent CT or TR groups that followed IN protocol; striped gray bars represent CT or TR groups that followed UN protocol.