Presynaptic GABA_B receptors reduce transmission at parabrachial synapses in the lateral central amygdala by inhibiting N-type calcium channels

摘要

The nocioceptive information carried by neurons of the pontine parabrachial nucleus to neurons of the lateral division of the central amydala (CeA-L) is thought to contribute to the affective components of pain and is required for the formation of conditioned-fear memories. Importantly, excitatory transmission between parabrachial axon terminals and CeA-L neurons can be inhibited by a number of presynaptic receptors linked to Gi/o-type G-proteins, including α2-adrenoceptors and GABA_B receptors. While the intracellular signalling pathway responsible for α2-adrenoceptor inhibition of synaptic transmission at this synapse is known, the mechanism by which GABA_B receptors inhibits transmission has not been determined. The present study demonstrates that activation of presynaptic GABA_B receptors reduces excitatory transmission between parabrachial axon terminals and CeA-L neurons by inhibiting N-type calcium channels. While the involvement of G_βγ subunits in mediating the inhibitory effects of GABA_B receptors on N-type calcium channels is unclear, this inhibition does not involve G_βγ-independent activation of pp60C-src tyrosine kinase. The results of this study further enhance our understanding of the modulation of the excitatory input from parabrachial axon terminals to CeA-L neurons and indicate that presynaptic GABA_B receptors at this synapse could be valuable therapeutic targets for the treatment of fear- and pain-related disorders.