Role for G Protein G_beta_gamma Isoform Specificity in Synaptic Signal Processing: A Computational Study

Richard Betram, Michelle I. Arnot, Gerald W. Zamponi

Computational modeling is used to investigate the functional impact of G protein-mediated presynaptic autoinhibition on synaptic filtering properties. It is demonstrated that this form of autoinhibition, which is relieved by depolarization, acts as a high-pass filter. This contrasts with vesicle depletion which acts as a low-pass filter. Model parameters are adjusted to reproduce kinetic slowing data from different G_beta_gamma dimeric isoforms, which produce different degrees of slowing. With these sets of parameter values, we demonstrate that the range of frequencies filtered out by the autoinhibition varies greatly depending on the G_beta_gamma isoform activated by the autoreceptors. It is shown that G protein autoinhibition can enhance the spatial contrast between a spatially distributed high-frequency signal and surrounding low-frequency noise, providing an alternate mechanism to lateral inhibition. It is also shown that autoinhibition can increase the fidelity of coincidence detection by increasing the signal to noise ratio in the postsynaptic cell. The filter cut, the input frequency below which signals are filtered, depends on several biophysical parameters in addition to those related to G_beta_gamma binding and unbinding. By varying one such parameter, the rate at which transmitter unbinds from autoreceptors, we show that the filter cut can be adjusted up or down for several of the G_beta_gamma isoforms. This allows for great synapse-to-synapse variability in the distinction between signal and noise.