Lesions of the basal amygdala block expression of conditioned fear but not extinction

Abstract

Although the role of the amygdala in acquisition of conditioned fear is well established, there is debate concerning the intra-amygdala circuits involved. The lateral nucleus of the amygdala (LA) is thought to be an essential site of plasticity in fear conditioning. The LA has both direct and indirect [via the basal nuclei; basal amygdala (BA)] projections to the central nucleus (Ce) of the amygdala, an essential output for fear behaviors. Lesions of the LA or Ce prevent acquisition of conditioned freezing to a conditioned stimulus, but BA lesions do not, suggesting that the BA is not normally involved in fear conditioning. If true, posttraining BA lesions should also have no effect. Replicating previous studies, we found that rats given electrolytic BA lesions before training acquired conditioned fear normally. They also showed normal long-term retention and extinction of conditioned fear. Unexpectedly, BA lesions made after training completely blocked expression of conditioned fear. Despite this deficit, lesioned rats were able to learn a new tone-shock association. Thus, although the LA-Ce system is sufficient for fear acquisition in the absence of the BA, it is not sufficient when the BA is present, suggesting that the BA is an important site of plasticity in fear conditioning. The pattern of lesion deficits we observed (after but not before training) might be explained by homeostatic mechanisms that balance plasticity over multiple inputs, regulating the influence of the BA and LA onto Ce output neurons.

Figure 1.

Examples of electrolytic BA lesions. A, The BA was defined to include the BL, BM, and AB nuclei, modified from Paxinos and Watson (1998). B, Micrograph showing a representative BA lesion. C, Coronal sections through the rostrocaudal extent of the amygdala in the three experimental groups: (1) pretraining lesions; (2) posttraining lesions; (3) pretraining lesions with delay. The smallest lesion is represented by the dark shading, whereas the largest lesion is outlined but not shaded. CE, Central nucleus; LA, lateral nucleus.

Figure 2.

Pretraining BA lesions had no effect on conditioning or extinction, but posttraining lesions blocked recall of conditioned fear. A, Percentage of freezing to the tone (top) and suppression of bar pressing (bottom) for BA-lesioned rats (n = 8) and sham-operated rats (n = 11). Pretraining BA lesions had no effect on acquisition or extinction of conditioned fear. The groups were not statistically different in any phase. B, Percentage of freezing to the tone (top) and suppression ratio (bottom) for BA-lesioned rats (n = 9) and sham-operated rats (n = 13). Postconditioning BA lesions blocked expression of conditioned fear. Blocks of two trials are plotted. Error bars indicate SEM. Hab, Habituation; Cond, conditioning; d1, d2, and d10, days 1, 2, and 10, respectively; L, lesion.

Figure 3.

Rats with posttraining BA lesions were able to recondition. A, A subset of lesioned (n = 6) and sham-operated (n = 7) rats shown in Figure 2 B were reconditioned with a new tone CS (1 kHz). Both groups conditioned to the new tone, ruling out damage to the LA as the cause of blocked expression (blocks of two trials are plotted). B, Rates of conditioning (day 1) and reconditioning (day 18) are compared for sham-operated (top) and BA-lesioned (bottom) rats. In both groups, savings was observed in the rate of reconditioning, suggesting generalization between tones and some degree of preserved memory in lesioned rats. Error bars indicate SEM. Hab, Habituation; Cond, conditioning; Recond, reconditioning; d1, d2, d10, and d18, days 1, 2, 10, and 18, respectively; L, lesion.

Figure 4.

Rats with pretraining BA lesions could retain fear memory for 8 d. The percentages offreezing to the tone on test days 2 and 10 for the pretraining with delay (left) and post training (right) experiments are shown. Rats with pretraining BA lesions (n = 5) could retain conditioning memory for 8 d, ruling out the passage of time after recovery from surgery as the cause of blocked expression with posttraining lesions. Error bars indicate SEM. L, lesion.

Figure 5.

Model to account for deficits with posttraining, but not pretraining, lesions. We suggest that homeostatic mechanisms that balance plasticity over multiple inputs could regulate the influence of the BA, LA, and MGm onto CeM neurons. 1, The CeM receives inputs from the MGm, BA, and LA via ITC cells (dashed line). 2, After fear conditioning, BA inputs gain a large proportion of the total plasticity, inhibiting the development of plasticity in neighboring inputs. 3, Posttraining lesions of the BA remove this plasticity, leaving the system subthreshold for producing a fear response. 4, With pretraining removal of the BA, however, increased plasticity in the LA and MGm supports fear learning. For simplicity, projections from the MGm to the LA and from the LA to the BA are not shown.