Synergism at central synapses due to lateral diffusion of transmitter

Recordings of inhibitory postsynaptic currents in the goldfish (Carassius auratus) Mauthner cell demonstrate nonlinear interactions when adjacent synapses are coactivated. Responses evoked by single presynaptic neurons were paired with those due to activation of a limited pool of similar inhibitory cells. In about 50% of the experiments the compound currents were substantially larger than the sum of their individual components. Potentiation was maximal when the two responses occurred nearly simultaneously, and its decay paralleled that of the conditioning current; it started with a delay of about 300 microsec, and calculations indicate that in this time transmitter molecules would diffuse laterally 0.5-1.1 micron, which equals the separation of adjacent synapses. Iontophoretically applied glycine produced a comparable enhancement of the eighth nerve evoked inhibitory current. When quantal inhibitory responses were simulated, taking into consideration glycine diffusion, transmitter-receptor interactions, and channel activation, with the latter requiring two binding steps, the results demonstrated that the facilitation when neighboring inputs are active is due to lateral diffusion of the transmitter, glycine, to fringe areas where single bound receptors are available for further interactions and channel opening.