Facilitation at the lobster neuromuscular junction: a stimulus-dependent mobilization model

Frequency facilitation is a process whereby neurosecretion increases as a function of stimulation frequency during repetitive synaptic activity. To examine the physiological basis underlying facilitation, we have estimated the frequency dependence of the synaptic parameters n (number of units capable of responding to a nerve impulse) and P (average probability of responding) at the lobster neuromuscular junction. Both n and P increase as a function of frequency, suggesting that the efficiency of quantal docking and quantal fusion is regulated by repetitive synaptic activity. In experiments in which facilitation is strong and quantal content does not saturate over the frequency range tested, the value of P saturates at low frequencies of stimulation, and increases in quantal content at higher frequencies of stimulation are due to an increase in n. Therefore the value of P does not limit facilitation. We propose that transmitter release is limited by the rates of quantal mobilization and demobilization, and that each excitatory stimulus causes additional mobilization of quanta to dock at the presynaptic release 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 facilitation predicts that the reciprocal value of the quantal content depends 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 that high rates of quantal demobilization will produce strong frequency facilitation.