A Blobby-controlled switch between Unc13 release modes shapes sensory decoding

Recent advances in connectomics have generated wiring diagrams of remarkable completeness, yet anatomical connectivity alone cannot predict synaptic dynamics or behavioral output because individual synapses differ profoundly in molecular composition and release properties. Isoforms of the release factor (M)Unc13 implement distinct release modes, exemplified in Drosophila by Unc13A and Unc13B, whose differential nanoscale positioning within active zones (AZs) produces divergent synaptic and behavioral outputs during olfactory processing. How synapses maintain the appropriate balance between isoform-specific release pathways remains unclear and requires a mechanistic framework linking molecular diversity to nanoscale organization. Here, we identify the RabGAP Blobby as a regulator of this balance. Blobby localizes to the distal edge of presynaptic AZs in excitatory projection neurons of the adult Drosophila olfactory system. Cell-type-specific manipulations show that Blobby loss phenocopies Unc13A reduction, delaying synaptic release and impairing both aversive and appetitive odor responses, whereas Blobby overexpression produces behavioral effects resembling Unc13B loss. Blobby reduction selectively increases Unc13B abundance and redistributes Unc13B toward central BRP-defined nanodomains. Correspondingly, reducing Unc13B rescues the behavioral deficits caused by Blobby loss. Together, these findings identify Blobby as a determinant of Unc13-isoform-specific release dynamics and reveal a regulatory layer shaping synapse identity, release-mode composition, and odor-driven behavior.