AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses

Silent synapses form between some primary sensory afferents and dorsal horn neurons in the spinal cord. Molecular mechanisms for activation or convers ion of silent synapses to conducting synapses are unknown. Serotonin can tr igger activation of silent synapses in dorsal horn neurons by recruiting AM PA receptors. AMPA-receptor subunits GluR2 and GluR3 interact via their cyt oplasmic C termini with PDZ-domain-containing proteins such as GRIP (glutam ate receptor interacting protein), but the functional significance of these interactions is unclear. Here we demonstrate that protein interactions inv olving the GluR2/3 C terminus are important for serotonin-induced activatio n of silent synapses in the spinal cord. Furthermore, PKC is a necessary an d sufficient trigger for this activation. These results implicate AMPA rece ptor-PDZ interactions in mechanisms underlying sensory synaptic potentiatio n and provide insights into the pathogenesis of chronic pain.