Aversive memory consolidation and reconsolidation: differences in neuro-transmitter engagement

Whether retrieval of a consolidated memory renders it fragile, and reconsolidation is required to keep the original memory are still open questions. We examined whether neuronal systems underlying consolidation in the basolateral amygdala (BLA) are required for recalled memories to persist. Experiments were done in compliance with the EU recommendations. Adult male Wistar rats received an electrical footshock in a conditioning apparatus (TC). After 7 days, rats were returned to the TC and freezing time was measured. A Na-channel blocker, tetrodotoxin (TTX, 5 ng), a H3 antagonist, thioperamide (44 pg), a muscarinic antagonist, scopolamine (50 µg), or AM251 (280 pg), a cannabinoid receptor 1 antagonist, were injected into the BLA. A 1st group was treated immediately after training on day 1. A 2nd group was injected 4 days after training without being reexposed to the TC, as well as a 3rd group that was reexposed to the TC immediately before drug treatments. In the 1st group ANOVA and “All Pairs Tukey-Kramer” test revealed that all drug-treated groups froze significantly less than controls (saline-injected) (F(4, 44) = 5.271; P < 0.05). In the 2nd group no drug-treatments caused significant change of freezing duration compared to saline. In the 3rd group AM251- and TTX-injected rats displayed a significant decrease of freezing time compared to all other groups (ANOVA and “All Pairs TukeyKramer” test F(4,51) = 5.582; P < 0.05). This report shows that reactivated fear memories return sensitive to pharmacological treatments that produce amnesia. TTX demonstrates that BLA neuronal activity is required for fear memory consolidation and reconsolidation, but cannabinoids control both processes, whereas cholinergic and histaminergic neurons only consolidation. The lability of retrieved memory affords opportunities to treat disorders, such as posttraumatic stress or chronic pain, and these results help searching for therapeutic targets to erase stubborn memories.