UCLA

Pavlovian fear conditioning is the predominant procedure used to study fear learning in rodents. Decades of research has shown that disrupting activity in the basolateral amygdala (BLA) attenuates the acquisition and storage of fear memories. As a result, current models of fear learning posit that information about the stimuli and aversive event converge and are stored in the BLA. Per this theory, the BLA should be necessary during both the tone and the shock to form this association. To test this theory, experiment 1 took advantage of the temporal specificity of optogenetics and inhibited the BLA during only the tone or only the shock of Pavlovian fear conditioning. The results show that BLA inhibition during the tone, but not the shock, disrupted fear learning and memory, calling into question the necessity of the BLA for processing the shock. Prior experience has a marked effect on future fear learning, but this research primarily focuses on the detrimental effect of stressful experience. The Sharpe lab recently began exploring how prior positive experiences influence fear learning. They found that the lateral hypothalamus (LH) becomes necessary for fear conditioning after reward learning experience. Experiment 2 investigated whether the BLA remain necessary to support fear learning and memory after LH is implicated in fear learning following reward experience. The BLA was optogenetically inhibited during the cue of fear conditioning in rats with or without reward experience. As expected, BLA inhibition disrupted fear memories in naïve rats. However, BLA inhibition did not affect fear memories in rats with reward learning experience. Experiment 3 investigated if brief optogenetic inhibition of the BLA in experiment 2 failed to disrupt the BLA at the crucial time to disrupt fear conditioning because the timescale of the BLA’s activity shifted. Using chemogenetics, the BLA was inhibited across acquisition of a tone-shock association in rats with or without reward experience. The results of experiment 3 were inconclusive due to insufficient expression of hm4di. Lastly, experiment 4 inhibited the BLA during fear conditioning in reward experienced rats with or without exposure to chronic unpredictable stress (CUS). Rats that received CUS treatment showed enhanced fear learning, but there was no difference in the effect of BLA inhibition during fear learning. Overall, these experiments demonstrate a new perspective on the canonical theory of fear learning and the BLA and expand on how the newfound role of LH in fear learning affects the importance of the BLA for this process and the importance of considering prior experience in our models of the neural circuits that drive learning and memory.