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

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 alpha 2-adrenoceptors and GABA(B) receptors. While the intracellular signalling pathway responsible for alpha 2-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(beta gamma) subunits in mediating the inhibitory effects of GABA(B) receptors on N-type calcium channels is unclear, this inhibition does not involve G(beta gamma)-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.