Aggressive behavior is regulated by various neuromodulators such as neuropeptides and biogenic amines. Here we found that the neuropeptide Drosulfakinin (Dsk) modulates aggression in Drosophila melanogaster. Knock-out of Dsk or Dsk receptor CCKLR-17D1 reduced aggression. Activation and inactivation of Dsk-expressing neurons increased and decreased male aggressive behavior, respectively. Moreover, data from transsynaptic tracing, electrophysiology and behavioral epistasis reveal that Dsk-expressing neurons function downstream of a subset of P1 neurons (P1a-splitGAL4) to control fighting behavior. In addition, winners show increased calcium activity in Dsk-expressing neurons. Conditional overexpression of Dsk promotes social dominance, suggesting a positive correlation between Dsk signaling and winning effects. The mammalian ortholog CCK has been implicated in mammal aggression, thus our work suggests a conserved neuromodulatory system for the modulation of aggressive behavior.

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Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, is one of the most popular herbal supplements. Numerous preclinical studies have shown the neuroprotective effects of EGb761 and support the notion that it may be effective in the treatment and prevention of neurodegenerative disorders such as Alzheimer’s disease (AD). Despite the preclinical promise, the clinical efficacy of this drug remains elusive. In this review, possible mechanisms underlying neuroprotective actions of EGb761 are described in detail, together with a brief discussion of the problem of studying this herb clinically to verify its efficacy in the treatment and prevention of AD. Moreover, various parameters e.g., the dosage and the permeability of the blood brain barrier (BBB), impacting the outcome of the clinical effectiveness of the extract are also discussed. Overall, the findings summarized in this review suggest that, a better understanding of the neuroprotective mechanisms of EGb761 may contribute to better understanding of the effectiveness and complexity of this herb and may also be helpful for design of therapeutic strategies in future clinical practice. Therefore, in future clinical studies, different factors that could interfere with the effect of EGb761 should be considered.