Fig. 1.

Signal transduction pathways for fear memory regulation. Memory destabilization or extinction after retrieval requires the activation of NMDA receptors (NMDAR) as the starting point; subsequent activation of L-type voltage-gated calcium channels (LVGCC), endogenous cannabinoid receptors (CB1), calcineurin, and finally proteasome-dependent protein degradation occurs. On the other hand, memory consolidation, reconsolidation, and consolidation of extinction memory (long-term extinction) require activation of transcription factor CREB-mediated transcription through phosphorylation at serine 133 by the activation of extracellular signal-regulated kinase/MAP kinase (ERK), protein A kinase (PKA), and/or Ca²⁺/calmodulin-dependent protein kinase IV (CaMKIV), which are downstream factors from cAMP and Ca²⁺ signal transduction