Transient changes in synaptic strength, known as short-term plasticity (STP), play a fundamental role in neuronal communication. Here, we present a protocol for using SRPlasticity, a software package that implements a computational model of STP. SRPlasticity supports automatic characterization of electrophysiological data and simulation of synaptic responses. We describe steps for installing and utilizing SRPlasticity, preprocessing data, fitting models, and simulating responses. We then detail procedures for analyzing spike response plasticity (SRP) model parameters to infer functional groupings of STP. For complete details on the use and execution of this protocol, please refer to Rossbroich et al.