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A model investigation of synaptic transmission tuned via the Unc13 protein.

Magdalena Springer1, Stephan Sigrist2, Martin Paul Nawrot1

1 University of Cologne
2 FU Berlin

Short-term synaptic plasticity is a fundamental mechanism in neural computation, influencing sensory adaptation and working memory on timescales ranging from milliseconds to minutes. At the molecular level, the interplay between two processes of vesicle release establishes the depressing and facilitating components at a single presynaptic site. The composition of short-term plasticity is driven by the expression of the gene variants (M)Unc13A and (M)Unc13B, which are evolutionary conserved across invertebrate and vertebrate species. In this study, we introduce a modification of the well-established Tsodyks-Markram model for short-term plasticity, incorporating independent facilitating and depressing model components. Our model is constrained through in vivo intracellular recordings within the olfactory pathway of Drosophila melanogaster, enabling accurate reproduction of postsynaptic responses towards dynamic presynaptic stimulation patterns. With our refined model, we emphasize the importance of the interplay between (M)Unc13A- and (M)Unc13B-dominated synapses in fine-tuning transmission dynamics. Moreover, analysis of the tuned parameter sets allows for comparison between different knock-down experiments, providing direct biological interpretability of the model parameters. Our findings contribute to the understanding the molecular basis of short-term plasticity in olfactory processing. Further, our fitted model can be utilized in future studies to design neural circuit models covering a highly realistic representation of protein-dependent short-term plasticity.