Universality vs. Specificity in Synaptic Transmission

Rapid and precise neuronal communication is enabled through a highly synchronous release of signaling molecules neurotransmitters within just milliseconds of the action potential. Yet neurotransmitter release lacked a theoretical framework that would be both phenomenologically accurate and mechanistically realistic. We present a statistical-mechanical analytic theory of the action-potential-triggered neurotransmitter release at the chemical synapse. The theory is demonstrated to be in detailed quantitative agreement with existing data on a wide variety of synapses from electrophysiological recordings in vivo and fluorescence experiments in vitro. Despite up to ten orders of magnitude of variation in the release rates among different synapses, the theory reveals that synaptic transmission obeys a simple, universal scaling law. The universality is demonstrated through a collapse of experimental data from strikingly diverse synapses onto a single, unifying master curve. The theory allows one to extract, directly from the experimental data, the molecular parameters that uniquely identify each synapse. The theory shows how functional characteristics of synapses – plasticity, fidelity, and efficacy – emerge from molecular properties of neurotransmitter release machinery.