Mice learn an association between footshock and optogenetic silencing of auditory cortical neurons. (A) Mice received 16 pairings of footshock with green light delivery to the auditory cortex. (B) The Arch/paired group (n = 10) showed freezing behavior in response to the light delivery (Arch/unpaired group, n = 7; EYFP/paired group, n = 7). (C) Averaged freezing time during five light ON epochs. One-way ANOVA, F2,21 = 16.9, P = 4.2 × 10−5. Tukey’s test, Arch paired vs. EYFP paired, ***P = 2.3 × 10−4; Arch paired vs. Arch unpaired, ***P = 2.2 × 10−4. (D) Light delivery induced a conditioned fear response even 30 d after conditioning, which was extinguished by repeated light delivery (n = 8). Repeated measures ANOVA, F30,210 = 17.1, P = 2.0 × 10−41.