SummaryLocal protein synthesis regulates the turning of growth cones to guidance cues yet little is known about which proteins are synthesized or how they contribute to directional steering. Here we show that β-actin mRNA resides in Xenopus retinal growth cones where it binds to the RNA-binding protein, Vg1RBP. Netrin-1 induces the movement of Vg1RBP granules into filopodia suggesting that it may direct the localization and translation of mRNAs in growth cones. Indeed, a gradient of netrin-1 activates the translation initiation regulator, eIF4E-BP, asymmetrically and triggers a polarized increase in β-actin translation on the near side of the growth cone prior to growth cone turning. Inhibition of β-actin translation abolishes both the asymmetric rise in β-actin and attractive, but not repulsive, turning. Our data suggest that newly synthesized β-actin, concentrated near sites of signal reception, provides the directional bias for polymerizing actin in the direction of an attractive stimulus.

Summary Sparse coding may be a general strategy of neural systems to augment memory capacity. In Drosophila, sparse odor coding by the Kenyon cells of the mushroom body is thought to generate a large number of precisely addressable locations for the storage of odor-specific memories. However, it remains untested how sparse coding relates to behavioral performance. Here we demonstrate that sparseness is controlled by a negative feedback circuit between Kenyon cells and the GABAergic anterior paired lateral (APL) neuron. Systematic activation and blockade of each leg of this feedback circuit show that Kenyon cells activate APL and APL inhibits Kenyon cells. Disrupting the Kenyon cell-APL feedback loop decreases the sparseness of Kenyon cell odor responses, increases inter-odor correlations, and prevents flies from learning to discriminate similar, but not dissimilar, odors. These results suggest that feedback inhibition suppresses Kenyon cell activity to maintain sparse, decorrelated odor coding and thus the odor-specificity of memories.

Mating elicits profound behavioral and physiological changes in many species that are crucial for reproductive success. After copulation, Drosophila melanogaster females reduce their sexual receptivity and increase egg laying [1, 2]. Transfer of male sex peptide (SP) during copulation mediates these postmating responses [1, 3-6] via SP sensory neurons in the uterus defined by coexpression of the proprioceptive neuronal marker pickpocket (ppk) and the sex-determination genes doublesex (dsx) and fruitless (fru) [7-9]. Although neurons expressing dsx downstream of SP signaling have been shown to regulate postmating behaviors [9], how the female nervous system coordinates the change from pre- to postcopulatory states is unknown. Here, we show a role of the neuromodulator octopamine (OA) in the female postmating response. Lack of OA disrupts postmating responses in mated females, while increase of OA induces postmating responses in virgin females. Using a novel dsx(FLP) allele, we uncovered dsx neuronal elements associated with OA signaling involved in modulation of postmating responses. We identified a small subset of sexually dimorphic OA/dsx(+) neurons (approximately nine cells in females) in the abdominal ganglion. Our results are consistent with a model whereby OA neuronal signaling increases after copulation, which in turn modulates changes in female behavior and physiology in response to reproductive state.

SummaryTaking advantage of the well-characterized olfactory system of Drosophila, we derive a simple quantitative relationship between patterns of odorant receptor activation, the resulting internal representations of odors, and odor discrimination. Second-order excitatory and inhibitory projection neurons (ePNs and iPNs) convey olfactory information to the lateral horn, a brain region implicated in innate odor-driven behaviors. We show that the distance between ePN activity patterns is the main determinant of a fly’s spontaneous discrimination behavior. Manipulations that silence subsets of ePNs have graded behavioral consequences, and effect sizes are predicted by changes in ePN distances. ePN distances predict only innate, not learned, behavior because the latter engages the mushroom body, which enables differentiated responses to even very similar odors. Inhibition from iPNs, which scales with olfactory stimulus strength, enhances innate discrimination of closely related odors, by imposing a high-pass filter on transmitter release from ePN terminals that increases the distance between odor representations.