Octopamine signals coordinate the spatial pattern of presynaptic machineries in the Drosophila mushroom bodies

Neurons need to adjust synaptic output according to the targets. However, the intracellular heterogeneity of synaptic machinery is scarcely reported in the central nervous system, and its regulatory mechanism remain unknown. Applying the CRISPR/Cas9-mediated split-GFP tagging, we devised cell-type specific fluorescent labeling of the endogenous active zone scaffold protein, Bruchpilot (Brp). This technology enabled the quantification of intracellular diversity of presynaptic structures within the Kenyon cells of the Drosophila mushroom bodies. We found that the accumulation of Brp at active zones is strikingly heterogenous among the compartments of Kenyon cell axon terminals. Mechanistically, the localized octopaminergic signaling along Kenyon cell terminals regulate the Brp heterogeneity via Octβ2R and cAMP signaling. We further found that acute food deprivation reduced the compartmental heterogeneity of Brp accumulation in an octopaminergic signaling-dependent manner. This synaptic regulation explains how the mushroom body integrates changing physiological states.