FACILITATION AT THE LOBSTER NEUROMUSCULAR-JUNCTION - A STIMULUS-DEPENDENT MOBILIZATION MODEL

Frequency facilitation is a process whereby neurosecretion increases a s a function of stimulation frequency during repetitive synaptic activ ity. To examine the physiological basis underlying facilitation, we ha ve estimated the frequency dependence of the synaptic parameters n (nu mber of units capable of responding to a nerve impulse) and P (average probability of responding) at the lobster neuromuscular junction. Bot h n and P increase as a function of frequency, suggesting that the eff iciency of quantal docking and quantal fusion is regulated by repetiti ve synaptic activity. in experiments in which facilitation is strong a nd quantal content does not saturate over the frequency range tested, the value of P saturates at low frequencies of stimulation, and increa ses in quantal content at higher frequencies of stimulation are due to an increase in n. Therefore the value of P does not limit facilitatio n. We propose that transmitter release is limited by the rates of quan tal mobilization and demobilization, and that each excitatory stimulus causes additional mobilization of quanta to dock at the presynaptic r elease sites. In such a model the binomial parameter n will correspond to the number of quanta docked at the release sites and available for release. We have developed and solved kinetic equations that describe how the number of docked quanta changes as a function of time and of stimulation frequency. The stimulus-dependent mobilization model of fa cilitation predicts that the reciprocal value of the quantal content d epends linearly on the reciprocal product of the stimulation frequency and the probability of release. Fits of the experimental data confirm the accuracy of this prediction, showing that the model proposed here quantitatively describes frequency facilitation. The model predicts t hat high rates of quantal demobilization will produce strong frequency facilitation.