Retrieval and extinction of remotely acquired fear are mediated by increased and decreased PKA activity and CREB phosphorylation, respectively. A, Top, Freezing levels during the final extinction session for each group. Bottom, the number of pCREB+ cells in RSC was increased relative to naive mice after 3 d, and returned to baseline levels after 6 d, of extinction training, mirroring the differences in freezing between the day 3 and day 6 groups. B, Representative sections showing immunostaining of pCREB+ cells in layer 2/3 of RSC. Scale bar, 125 μm. C, Inhibition of PKA via Rp-cAMPS blocked retrieval of remote fear memory. D, Inhibition of PKA facilitated extinction of remotely acquired fear. E, Activation of PKA via 8-Br-cAMPs blocked remote extinction. F, Remote extinction was unaffected by infusions of the β-receptor antagonist nadolol or the D1 receptor antagonist SCH23390. Arrows indicate post-extinction infusions; *p < 0.05.