PT - JOURNAL ARTICLE AU - Lana Inoue AU - Thomas Michael Ernst AU - Inda Inat Ferber AU - Christian Josef Merz AU - Dagmar Timmann AU - Giorgi Batsikadze TI - Interaction of fear conditioning with eyeblink conditioning supports the sensory gating hypothesis of the amygdala in men AID - 10.1523/ENEURO.0128-20.2020 DP - 2020 Sep 03 TA - eneuro PG - ENEURO.0128-20.2020 4099 - http://www.eneuro.org/content/early/2020/09/02/ENEURO.0128-20.2020.short 4100 - http://www.eneuro.org/content/early/2020/09/02/ENEURO.0128-20.2020.full AB - Inhibition of the amygdala slows down acquisition of conditioned eyeblink responses (CRs). Based on the two-stage or two-factor theory of aversive conditioning, amygdala-dependent conditioned fear is a necessary prerequisite to acquire eyeblink CRs, but is no longer needed after eyeblink CRs are attained. According to the sensory gating hypothesis of the amygdala, on the other hand, the amygdala modulates the salience of unconditioned and conditioned stimuli (US and CS) in eyeblink conditioning. We tested these two opposing assumptions in five groups of 20 young and healthy men. On day 1, three groups underwent fear acquisition training followed by acquisition of eyeblink CRs. On the next day (day 2), extinction was tested. In Group 1, fear and eyeblink extinction trials overlapped; in Group 2, fear and eyeblink extinction trials alternated; and in Group 3, fear extinction trials were followed by eyeblink extinction trials. Groups 4 and 5 were control conditions testing fear and eyeblink conditioning only. Preceding fear acquisition training facilitated acquisition of conditioned eyeblinks. Concomitant fear extinction impeded extinction of eyeblink CRs, which was accompanied by increased autonomic responses. Fear extinction, however, was not significantly altered by concomitant eyeblink extinction. Recall of fear CRs on day 2 was facilitated in Group 1 suggesting additive response summation. Findings are difficult to explain with the two-stage theory of aversive conditioning which predicts suppression of conditioned fear once conditioned eyeblinks are acquired. Facilitated acquisition and impeded extinction of eyeblink CRs, however, are in accordance with the sensory gating hypothesis of the amygdala.Significance Statement It has been proposed that conditioned eyeblink responses, once established, may help to facilitate fear extinction. This has potential clinical relevance because extinction of learned fear responses is at the core of exposure therapy in the treatment of many anxiety disorders. Based on our findings this proposal has to be rejected. Our findings do not support the two-stage theory of aversive conditioning which predicts suppression of conditioned fear once conditioned eyeblinks are acquired. Rather, we found that concomitant extinction of conditioned eyeblink and fear responses facilitated recall of conditioned fear responses, and impeded extinction of conditioned eyeblinks. Findings are best explained by increased salience of conditioned stimuli, and therefore support the sensory gating hypothesis of the amygdala.