Mated females reallocate resources to offspring production, causing changes to nutritional requirements and challenges to energy homeostasis. Although observed across species, the neural and endocrine mechanisms that regulate the nutritional needs of mated females are not well understood. Here, we find that mated Drosophila melanogaster females increase sugar intake, which is regulated by the activity of sexually dimorphic insulin receptor (Lgr3) neurons. In virgins, Lgr3+ cells have reduced activity as they receive inhibitory input from active, female specific pCd-2 cells, restricting sugar intake. During copulation, males deposit sex peptide into the female reproductive tract, which silences a three-tier mating status circuit and initiates the female postmating response. We show that pCd-2 neurons also become silenced after mating due to the direct synaptic input from the mating status circuit. Thus, in mated females pCd-2 inhibition is attenuated, activating downstream Lgr3+ neurons and promoting sugar intake. Together, this circuit transforms the mated signal into a long-term hunger signal. Our results demonstrate that the mating circuit alters nutrient sensing centers to increase feeding in mated females, providing a mechanism to increase intake in anticipation of the energetic costs associated with reproduction.
All data generated and analyzed during this study are included in the manuscript and supporting files
- Kristin Scott
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Sonia Sen, Tata Institute for Genetics and Society, India
© 2023, Laturney et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The amyloid beta (Aβ) plaques found in Alzheimer’s disease (AD) patients’ brains contain collagens and are embedded extracellularly. Several collagens have been proposed to influence Aβ aggregate formation, yet their role in clearance is unknown. To investigate the potential role of collagens in forming and clearance of extracellular aggregates in vivo, we created a transgenic Caenorhabditis elegans strain that expresses and secretes human Aβ1-42. This secreted Aβ forms aggregates in two distinct places within the extracellular matrix. In a screen for extracellular human Aβ aggregation regulators, we identified different collagens to ameliorate or potentiate Aβ aggregation. We show that a disintegrin and metalloprotease a disintegrin and metalloprotease 2 (ADM-2), an ortholog of ADAM9, reduces the load of extracellular Aβ aggregates. ADM-2 is required and sufficient to remove the extracellular Aβ aggregates. Thus, we provide in vivo evidence of collagens essential for aggregate formation and metalloprotease participating in extracellular Aβ aggregate removal.
The cerebellar granule cell layer has inspired numerous theoretical models of neural representations that support learned behaviors, beginning with the work of Marr and Albus. In these models, granule cells form a sparse, combinatorial encoding of diverse sensorimotor inputs. Such sparse representations are optimal for learning to discriminate random stimuli. However, recent observations of dense, low-dimensional activity across granule cells have called into question the role of sparse coding in these neurons. Here, we generalize theories of cerebellar learning to determine the optimal granule cell representation for tasks beyond random stimulus discrimination, including continuous input-output transformations as required for smooth motor control. We show that for such tasks, the optimal granule cell representation is substantially denser than predicted by classical theories. Our results provide a general theory of learning in cerebellum-like systems and suggest that optimal cerebellar representations are task-dependent.