Model systems of synaptic organization in the Drosophila olfactory circuit. a) Micrograph of an adult Drosophila brain stained with a general neurite label (blue) and a marker that reveals the mushroom body (MB) lobes (magenta). The anatomical locations of the antennal lobe (AL; dashed box) and MB (solid box) are indicated. b) Schematic of the fly brain with annotated olfactory circuit [figure panel modeled after Schlegel et al. (2021)]. Odor information flows from the antennae and maxillary palps to the first-order processing center, the AL (shown in green). Olfactory information is then transmitted to higher order brain regions, including the MB shown in blue and the lateral horn (LH). The AL is organized into discrete neuropil where 3 major neuronal classes form synaptic connections (inset shows 3 anatomically distinct neuropil: DA1, VA1d, and VA1v). c) Micrograph of AL glomeruli corresponding to the region indicated in the dashed box in (b). All ORNs that express a particular OR (Or67d) converge on a single glomerulus (Dashed; DA1). Restricted expression of Brp-Short::mStrawberry in these ORNs reveals AZ distribution. d) Three major neuronal classes reside in each AL glomeruli [figure modeled after Cachero and Jefferis (2008)]. A single glomerulus is diagrammed in (d) where ORN are presynaptic to PNs. PNs then transmit odorant information to higher-order brain regions including the MB and LH. The LNs comprise many different classes of cells defined by morphology and form an extensive lateral network that connects most or all glomeruli. LNs form synaptic connections with ORNs, PNs, and other LNs. e) Synaptic organization in the AL is regulated by the Teneurin and LRP4 signaling pathways [figure adapted from DePew et al. (2019) and DePew and Mosca (2021)]. Trans-synaptic heterophilic Teneurin interactions instruct synaptic organization in the AL. Presynaptic Ten-a functions with Spectrin to promote presynaptic AZ assembly and organization. The role of postsynaptic Ten-m remains unknown. In addition to the Teneurins, LRP4 function is required to maintain normal synaptic organization in the AL. The current model of LRP4 function posits that LRP4 recruits SRPK79D (SRPK) to the synapse where these 2 regulate synaptic assembly and morphology. f) Micrograph of MB lobes (magenta). MB calyces are not discernible. g) Schematic of the MB. The MB intrinsic neurons, the Kenyon cells (KCs), concentrate their dendrites in the calyx and send axonal projections in parallel bundles to form the MB lobes. g”) KC dendrites are mixed neurites that exhibit both pre- and postsynaptic specializations [figure adapted from Christiansen et al. (2011)]. KCs are postsynaptic to olfactory PNs and form specialized “dendritic claws” that can be labeled with the acetylcholine receptor subunit Dα7::GFP (Green in inset; cartoon modeled after; Kremer et al. 2010). KC-derived presynaptic AZs form outside of the dendritic claws (arrowheads in inset).