A developmental switch in neurotransmitter flux enhances synaptic efficacyby affecting AMPA receptor activation

Formation of glutamatergic synapses entails development of "silent" immatur e contacts into mature functional synapses. To determine how this transform ation occurs, we investigated the development of neurotransmission at singl e synapses in vitro. Maturation of presynaptic function, assayed with endoc ytotic markers, followed accumulation of synapsin 1. During this period, sy naptic transmission was primarily mediated by activation of NMDA receptors, suggesting that most synapses were functionally silent. However, local glu tamate application to silent synapses indicated that these synapses contain ed functional AMPA receptors, suggesting a possible presynaptic locus for s ilent transmission. Interference with presynaptic vesicle fusion by exposur e to tetanus toxin reverted functional to silent transmission, implicating SNARE-mediated fusion as a determinant of the ratio of NMDA:AMPA receptor a ctivation. This work reveals that functional maturation of synaptic transmi ssion involves transformation of presynaptic silent secretion into mature s ynaptic transmitter release.