Baclofen acts in the central amygdala to reduce synaptic transmission and impair context fear conditioning

The two main sub-divisions of the Central amygdala (CeA), the lateral-capsular (CeA-LC) and the medial (CeA-M), contain extensive networks of inhibitory interneurons. We have previously shown that activation of GABA(B)-receptors reduces excitatory transmission between axons of the pontine parabrachial nucleus and neurons of the CeA-LC by inhibiting glutamate release from presynaptic terminals(13). Here we have characterised GABA(B)-receptor activation on other excitatory and inhibitory projections within the CeA. Using whole-cell, patch-clamp recordings, we found that the GABA(B)-receptor agonist baclofen significantly reduced excitatory and inhibitory transmission from all tested inputs into the CeA-LC and CeA-M. In all but one of the inputs, reductions in transmission were accompanied by an increase in paired pulse ratio, indicating that presynaptic GABA(B)-receptors acted to reduce the release probability of synaptic vesicles. To examine the impact of GABA(B)-receptors in the CeA on contextual fear-conditioning, we infused baclofen into the CeA immediately prior to training. Compared to vehicle-infused rats, baclofen-infused rats displayed significantly less freezing both during the final stages of the training period and at test 24 hours later. The results of this study demonstrate that, by suppressing excitatory and inhibitory transmission, activation of presynaptic GABA(B)-receptors in the CeA inhibits the development of context conditioned fear.