Internal mechanosensory feedback modulates central pattern generation to coordinate ovulation in Drosophila

Abstract

Ovulation is a prerequisite for successful reproduction and requires precise coordination of muscle contractions, especially to propel eggs from the paired lateral oviducts into the common oviduct. Although internal mechanosensation is expected to provide critical feedback for this process, the sensorimotor circuitry and mechanisms by which sensory feedback shapes motoneuron activity and coordinates oviduct contractions are still poorly known. Here, in Drosophila, we identify a novel pair of multidendritic mechanosensory neurons (mdn-LO) in the lateral oviducts that express the mechanosensitive channels TMC (transmembrane channel-like protein), PPK (pickpocket), and Piezo. We show that TMC is essential for coordinated ovulation; tmc mutation or neuron-specific knockdown increases egg-jamming at the junction between the lateral and the common oviduct. In contrast, ppk or Piezo mutants display reduced egg-laying but no jamming. Calcium imaging reveals that the mdn-LO neurons are rhythmically activated by oviduct contractions, and chemogenetic stimulation of these neurons triggers muscle contractions. Genetic manipulations of the mdn-LO neurons disrupt egg passage and induce egg-jamming. The axons of the mdn-LO neurons form functional contacts with female-specific oviduct motoneurons in the abdominal neuromeres that express insulin-like peptide 7 (ILP7) and glutamate. Activation of mdn-LO neurons triggers Ca{superscript 2} activity in ILP7 motoneurons and elicits rhythmic oviduct contractions. Importantly, the ILP7 motoneurons exhibit spontaneous rhythmic Ca{superscript 2} activity that is modulated by oviduct contractions and egg movement. Furthermore, triggering activity in the ILP7 neurons induces egg-jamming. Finally, knockdown of ILP7 peptide affects the rate of ovulation, but plays no role in egg jamming, which instead is likely induced by colocalized glutamate. In summary, our study identifies a novel circuit, including the TMC-expressing mdn-LO neurons and a small set of ILP7 motoneurons, that organizes an innate behavior by coupling strategic sensory information and rhythmical motor output to ensure bilateral coordination of oviduct contractions to prevent egg jamming during oviposition. SignificanceOvulation requires precisely coordinated contractions of the lateral oviducts to propel eggs into the common oviduct without jamming. Yet the sensory cells and mechanotransduction channels that coordinate movement through the paired lateral oviducts remain unclear. Here, we identify a novel pair of lateral-oviduct multidendritic neurons (mdn-LO) that express the conserved mechanosensory channels TMC (transmembrane channel-like protein), PPK (pickpocket), and Piezo, and show that TMC is uniquely required to prevent egg jamming at the junction between the lateral and common oviducts. The mdn-LO neurons are activated by oviduct contractions and relay signals to female-specific glutamatergic motoneurons in the abdominal neuromere. These paired oviduct motoneurons are rhythmically active and regulate contractions of the lateral oviducts. Together, our findings demonstrate that TMC-mediated mechanosensory feedback fine-tunes motor output to ensure coordinated ovulation and successful reproduction.