Updating appetitive memory during reconsolidation window: critical role of cue-directed behavior and amygdala central nucleus

Abstract

When presented with a light cue followed by food, some rats simply approach the foodcup (Nonorienters), while others first orient to the light in addition to displaying the food-cup approach behavior (Orienters). Cue-directed orienting may reflect enhanced attentional and/or emotional processing of the cue, suggesting divergent natures of cue-information processing in Orienters and Nonorienters. The current studies investigate how differences in cue processing might manifest in appetitive memory retrieval and updating using a paradigm developed to persistently attenuate fear responses (Retrieval-extinction paradigm; Monfils et al., 2009). First, we examined whether the retrieval-extinction paradigm could attenuate appetitive responses in Orienters and Nonorienters. Next, we investigated if the appetitive memory could be updated using reversal learning (fear conditioning) during the reconsolidation window (as opposed to repeated unreinforced trials, i.e., extinction). Both extinction and new fear learning given within the reconsolidation window were effective at persistently updating the initial appetitive memory in the Orienters, but not the Nonorienters. Since conditioned orienting is mediated by the amygdala central nucleus (CeA), our final experiment examined the CeA's role in the retrieval-extinction process. Bilateral CeA lesions interfered with the retrieval-extinction paradigm-did not prevent spontaneous recovery of food-cup approach. Together, our studies demonstrate the critical role of conditioned orienting behavior and the CeA in updating appetitive memory during the reconsolidation window.

Keywords: appetitive learning; central amygdala; conditioned orienting; extinction; fear learning.

Figure 1

Mean (±SEM) OR (A) and food-cup response (B) during training. OR bouts were measured during the first 5 s of each CS and food-cup entries were measured during the last 5 s CS period. The values shown are elevation scores, calculated by subtracting pre-CS baseline responding from responding during the CS. Orienters, but not Nonorienters, acquired conditioned OR to the light CS, p < 0.0001 (A). In contrast, both Orienters and Nonorienters acquired conditioned food-cup responding (B).

Figure 2

Mean (±SEM) OR (A) and food cup response (B) during extinction. Orienters and Nonorienters refer to the animals that showed robust and no conditioned orienting, respectively, during conditioning phase. Ret refers to the extinction condition, in which a single CS was presented prior to regular extinction trials while No Ret refers to the regular extinction trials without a prior CS presentation. Orienters showed more OR than Nonorienters (A). There was no difference in food-cup responding among four groups, and all showed comparable extinction rates (B).

Figure 3

Mean (±SEM) OR (A) and food cup response (B) for Orienters (left panels) and Nonorienters (right panels). The values are responses during the last four CS alone presentations in extinction session, four CS alone presentation 24 h (test 1) and 21 days (test 2) after extinction. A single CS presentation 1 h prior to extinction trials (retrieval condition) blocked return of spontaneous food-cup response only in Orienters.

Figure 4

Mean (±SEM) OR (A) and food-cup response (B) during appetitive training, and freezing response during fear conditioning (C) and subsequent extinction trials (D). Orienter and Nonorienter designations refer to those rats that developed a robust OR during appetitive training (Orienters) and those that did not (Nonorienters). Ret refers to the condition in which rats received a single CS exposure 10 min prior to fear conditioning, while No ret designates those rats were only exposed to the conditioning context prior to fear conditioning. Both Orienters and Nonorienters acquired conditioned food cup response (B) while only Orienters showed conditioned OR (A). Both Orienters and Nonorienters achieved comparable freezing levels by the end of fear conditioning trials (C) and displayed similar extinction rates (D) regardless of retrieval condition. However, the Orienters-No Retrieval group showed slightly increased freezing levels both during acquisition and extinction trials.

Figure 5

Mean (±SEM) food cup response (A), OR (B) and freezing (C) during the appetitive reacquisition phase. Orienter and Nonorienter designations refer to those rats that developed a robust OR during the original appetitive training (Orienters) and those that did not (Nonorienters). Ret refers to the condition in which rats received a single CS exposure 10 min prior to fear conditioning while No ret designates those rats that did not (context exposure only). Only Orienters in the retrieval condition showed retarded reacquisition of conditioned food cup response (A), but intact reacquisition of conditioned OR (B) and no difference in the minimal levels of freezing (C).

Figure 6

Representative photomicrographs of the amygdala region from the animals with sham lesion (A) and ibotenic acid lesion (B). Central amygdala (CeA), stria terminalis (ST), intercalated nucleus (IC), and BLA are highlighted. Average lesion size was 65% CeA damage, and rats with significant BLA damage were excluded. (C) Mean (±SEM) OR and food cup response during the last eight trials of training for Orienters, Nonorienters, and Lesion rats. Animals with CeA lesions showed minimal conditioned OR, but still showed intact conditioned food-cup response. (D and E) Mean (±SEM) OR and food cup response during extinction. Orienters showed more OR than Nonorienters and CeA Lesioned rats at the beginning but at the end. There was no difference in food-cup responding among six groups, and all showed comparable extinction rates.

Figure 7

Mean (±SEM) food-cup responding during extinction and tests both 24-h (Test 1) and 21 days (Test 2) after extinction. The values are responses during the last two CS alone presentations of the extinction session, and the first two CS alone presentations during Test 1 and Test 2. Orienters in the retrieval condition are the only animals not showing spontaneous recovery of conditioned food-cup response.