Interplay between facilitation, depression, and residual calcium at three presynaptic terminals

Synapses display remarkable alterations in strength during repetitive use. Different types of synapses exhibit distinctive synaptic plasticity, but th e factors giving rise to such diversity are not fully understood. To provid e the experimental basis for a general model of short-term plasticity, we s tudied three synapses in rat brain slices at 34 degrees C: the climbing fib er to Purkinje cell synapse, the parallel fiber to Purkinje cell synapse, a nd the Schaffer collateral to CA1 pyramidal cell synapse. These synapses ex hibited a broad range of responses to regular and Poisson stimulus trains. Depression dominated at the climbing fiber synapse, facilitation was promin ent at the parallel fiber synapse, and both depression and facilitation wer e apparent in the Schaffer collateral synapse. These synapses were modeled by incorporating mechanisms of short-term plasticity that are known to be d riven by residual presynaptic calcium (Ca-res). In our model, release is th e product of two factors: facilitation and refractory depression. Facilitat ion is caused by a calcium-dependent increase in the probability of release . Refractory depression is a consequence of release sites becoming transien tly ineffective after release. These sites recover with a time course that is accelerated by elevations of Ca-res. Facilitation and refractory depress ion are coupled by their common dependence on Ca-res and because increased transmitter release leads to greater synaptic depression. This model captur es the behavior of three different synapses for various stimulus conditions . The interplay of facilitation and depression dictates synaptic strength a nd variability during repetitive activation. The resulting synaptic plastic ity transforms the timing of presynaptic spikes into varying postsynaptic r esponse amplitudes.