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.

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

“…Infusions of NMDAR antagonists targeted for the lateral nucleus (this study) or the basal nucleus (most previous studies) of the amygdala likely affect both regions, as well as the intercalated cell masses and the central nucleus (Paré et al, 2004). Although we cannot rule out an effect on regions surrounding the lateral amygdala in this study, given that lesions of the basal amygdala do not affect extinction learning (Sotres-Bayon et al, 2004;Anglada-Figueroa and Quirk, 2005), it seems likely that the lateral amygdala was the key subregion affected by previous studies. In addition, we used an infusion volume that was one-half of that used in most previous studies, and so our results more specifically implicate the lateral amygdala.…”

Concomitant Deficits in Working Memory and Fear Extinction Are Functionally Dissociated from Reduced Anxiety in Metabotropic Glutamate Receptor 7-Deficient Mice

“…This suggests that acquisition and extinction share a common mechanism, but Cain et al (2002) argued that the neuroplasticity underlying extinction involves L-type voltage-gated calcium channels rather than NMDA receptors. This and other evidence indicates that some processes underlying extinction might be distinct from those involved in acquisition or expression of fear responses (Cain et al, 2002;Barrett et al, 2003;Anglada-Figueroa and Quirk, 2005).…”

Mechanisms of fear extinction

“…This was considered possible because BA lesions have little if any effect upon the acquisition or expression of conditioned fear when the lesions are made before training. [90][91][92][93] When done before acquisition, BA lesions did not have an effect on the extinction of fear, leading to the suggestion that LA and not BA is the critical locus of amygdalar involvement in extinction. 72 When done after acquisition, however, BA lesions eliminated expression of conditioned fear, 91 making it impossible to determine an effect on extinction.…”

“…[90][91][92][93] When done before acquisition, BA lesions did not have an effect on the extinction of fear, leading to the suggestion that LA and not BA is the critical locus of amygdalar involvement in extinction. 72 When done after acquisition, however, BA lesions eliminated expression of conditioned fear, 91 making it impossible to determine an effect on extinction. What this seems to suggest is that BA normally is recruited during acquisition and contributes to the expression of conditioned fear, but in the absence of BA other regions are able to compensate.…”