Diffusion into the axon shapes presynaptic Ca2+ signals. (A) An illustration of the three major determinants of Ca2+ signals in en passant presynaptic boutons is shown. Tran and Stricker (8) found that, besides buffering and extrusion, diffusion into the axon significantly impacts Ca2+ transients. (B) In a single-compartment model, the endogenous Ca2+ dynamics can be back extrapolated from amplitudes and time constants of Ca2+ dye signals. (C) With increasing axon diameter, the Ca2+ decay accelerates, becomes biexponential, and contaminates τ back extrapolation of κ.