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3 Publications

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    Cardona Lab
    06/08/20 | The corazonin-PTTH neuronal axis controls systemic body growth by regulating basal ecdysteroid biosynthesis in Drosophila melanogaster.
    Imura E, Shimada-Niwa Y, Nishimura T, Hückesfeld S, Schlegel P, Ohhara Y, Kondo S, Tanimoto H, Cardona A, Pankratz MJ, Niwa R
    Current Biology. 2020 Jun 8;30(11):2156-65. doi: 10.1016/j.cub.2020.03.050

    Steroid hormones play key roles in development, growth, and reproduction in various animal phyla [1]. The insect steroid hormone, ecdysteroid, coordinates growth and maturation, represented by molting and metamorphosis [2]. In Drosophila melanogaster, the prothoracicotropic hormone (PTTH)-producing neurons stimulate peak levels of ecdysteroid biosynthesis for maturation [3]. Additionally, recent studies on PTTH signaling indicated that basal levels of ecdysteroid negatively affect systemic growth prior to maturation [4-8]. However, it remains unclear how PTTH signaling is regulated for basal ecdysteroid biosynthesis. Here, we report that Corazonin (Crz)-producing neurons regulate basal ecdysteroid biosynthesis by affecting PTTH neurons. Crz belongs to gonadotropin-releasing hormone (GnRH) superfamily, implying an analogous role in growth and maturation [9]. Inhibition of Crz neuronal activity increased pupal size, whereas it hardly affected pupariation timing. This phenotype resulted from enhanced growth rate and a delay in ecdysteroid elevation during the mid-third instar larval (L3) stage. Interestingly, Crz receptor (CrzR) expression in PTTH neurons was higher during the mid- than the late-L3 stage. Silencing of CrzR in PTTH neurons increased pupal size, phenocopying the inhibition of Crz neuronal activity. When Crz neurons were optogenetically activated, a strong calcium response was observed in PTTH neurons during the mid-L3, but not the late-L3, stage. Furthermore, we found that octopamine neurons contact Crz neurons in the subesophageal zone (SEZ), transmitting signals for systemic growth. Together, our results suggest that the Crz-PTTH neuronal axis modulates ecdysteroid biosynthesis in response to octopamine, uncovering a regulatory neuroendocrine system in the developmental transition from growth to maturation.

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    Truman LabCardona LabZlatic LabFlyLightFly Facility
    03/23/20 | Recurrent architecture for adaptive regulation of learning in the insect brain.
    Eschbach C, Fushiki A, Winding M, Schneider-Mizell CM, Shao M, Arruda R, Eichler K, Valdes-Aleman J, Ohyama T, Thum AS, Gerber B, Fetter RD, Truman JW, Litwin-Kumar A, Cardona A, Zlatic M, Cardona A, Zlatic M
    Nature Neuroscience. 2020 Mar 23;23(4):544-55. doi: 10.1038/s41593-020-0607-9

    Dopaminergic neurons (DANs) drive learning across the animal kingdom, but the upstream circuits that regulate their activity and thereby learning remain poorly understood. We provide a synaptic-resolution connectome of the circuitry upstream of all DANs in a learning center, the mushroom body of Drosophila larva. We discover afferent sensory pathways and a large population of neurons that provide feedback from mushroom body output neurons and link distinct memory systems (aversive and appetitive). We combine this with functional studies of DANs and their presynaptic partners and with comprehensive circuit modeling. We find that DANs compare convergent feedback from aversive and appetitive systems, which enables the computation of integrated predictions that may improve future learning. Computational modeling reveals that the discovered feedback motifs increase model flexibility and performance on learning tasks. Our study provides the most detailed view to date of biological circuit motifs that support associative learning.

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    Cardona LabFly Facility
    02/14/20 | Identifying neural substrates of competitive interactions and sequence transitions during mechanosensory responses in Drosophila.
    Masson J, Laurent F, Cardona A, Barre C, Skatchkovsky N, Zlatic M, Jovanic T
    PLoS Genetics. 2020 Feb 14;16(2):e1008589. doi: 10.1371/journal.pgen.1008589

    Nervous systems have the ability to select appropriate actions and action sequences in response to sensory cues. The circuit mechanisms by which nervous systems achieve choice, stability and transitions between behaviors are still incompletely understood. To identify neurons and brain areas involved in controlling these processes, we combined a large-scale neuronal inactivation screen with automated action detection in response to a mechanosensory cue in Drosophila larva. We analyzed behaviors from 2.9x105 larvae and identified 66 candidate lines for mechanosensory responses out of which 25 for competitive interactions between actions. We further characterize in detail the neurons in these lines and analyzed their connectivity using electron microscopy. We found the neurons in the mechanosensory network are located in different regions of the nervous system consistent with a distributed model of sensorimotor decision-making. These findings provide the basis for understanding how selection and transition between behaviors are controlled by the nervous system.

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