Matching Dynamics of Presynaptic and Postsynaptic Scaffolds

Synapses undergo substantial activity-dependent and independent remodeling over time scales of minutes, hours, and days. Presumably, changes in presynaptic properties should be matched by corresponding changes in postsynaptic properties and vice versa. Wherever measured, presynaptic and postsynaptic molecular properties tend to correlate, yet these correlations are often quite imperfect, raising questions as the origins of such mismatches: Are these the outcome of single snapshot analyses of asynchronous remodeling processes? Alternatively, do these indicate that synapses genuinely vary in the stoichiometries of their presynaptic and postsynaptic molecular contents? If so, are these stoichiometries preserved over time? To address these questions, we followed the matching dynamics of the presynaptic active-zone molecule Munc13-1 and the postsynaptic molecule PSD-95 in networks of cultured cortical mouse neurons. We find that presynaptic and postsynaptic remodeling were generally well correlated, but the degree of this correlation was highly variable, with little and even negative correlation observed at some synapses. No evidence was found that remodeling in one compartment consistently preceded remodeling in the other. Interestingly, even though the Munc13-1 and PSD-95 contents of individual synapses changed considerably over 15-22 h, Munc13-1/PSD-95 ratios, which varied over a fourfold range, were well conserved over these durations. These findings indicate that the stoichiometries of presynaptic and postsynaptic molecules can genuinely differ among synapses and that synapses can maintain their specific stoichiometries even in face of extensive presynaptic and postsynaptic remodeling.