Post-synaptic GABA(A) receptors potentiate transmission by recruiting CaV2 channels to their inputs.

We describe a retrograde synaptic signal at the C. elegans GABAergic neuromuscular junction. At this synapse, GABA release is controlled by two voltage-activated calcium channels (UNC-2/CaV2 and EGL-19/CaV1), and muscle responses are mediated by a single GABA receptor (UNC-49/GABA(A)). Mutations inactivating UNC-49 or those preventing UNC-49 synaptic clustering cause retrograde defects in GABAergic motor neurons, whereby UNC-2/CaV2 levels at active zones, UNC-2 current, and pre-synaptic GABA release are decreased. Inactivating post-synaptic GABA(A) receptors has no effect on GABA neuron EGL-19/CaV1 levels nor on several other pre-synaptic markers. The effect of GABA(A) receptors on pre-synaptic strength is not a consequence of decreased GABA transmission and is input selective. Finally, pre-synaptic UNC-2/CaV2 levels are increased when post-synaptic GABA(A) receptors are increased but are unaffected by increased extra-synaptic receptors. Collectively, these results suggest that clustered post-synaptic GABA(A) receptors adjust the strength of their inputs by recruiting CaV2 to contacting active zones.