Abstract

The neuronal mechanisms by which complex behaviors are coordinated and timed often involve neuropeptidergic regulation of stress and reward pathways. Recent studies of the neuropeptide Corazonin (Crz), a homolog of the mammalian Gonadotrophin Releasing Hormone (GnRH), have suggested its crucial role in the regulation of growth, internal states and behavioral decision making. We focus this review on Crz neurons with the goal to (1) highlight the diverse roles of Crz neuron function, including mechanisms that may be independent of the Crz peptide, (2) emphasize current gaps in knowledge about Crz neuron functions, and (3) propose exciting ideas of novel research directions involving the use of Crz neurons. We describe the different developmental fates of distinct subsets of Crz neurons, including recent findings elucidating the molecular regulation of apoptosis. Crz regulates systemic growth, food intake, stress responses and homeostasis by interacting with the short Neuropeptide F (sNPF) and the steroid hormone ecdysone. Additionally, activation of Crz neurons is shown to be pleasurable by interacting with the Neuropeptide F (NPF) and regulates reward processes such as ejaculation and ethanol-related behaviors in a sexually dimorphic manner. Crz neurons are proposed to be a motivational switch regulating copulation duration using a CaMKII-dependent mechanism described as the first neuronal interval timer lasting longer than a few seconds. Lastly, we propose ideas to use Crz neuron-induced ejaculation to study the effects of fictive mating and sex addiction in flies, as well as to elucidate dimorphic molecular mechanisms underlying reward behaviors and feeding disorders.

Highlights

  • Corazonin Neurons as a Hub for Regulating Growth, Stress Responses, Ethanol-Related Behaviors, Copulation Persistence and Sexually

  • Ecdysone binds to either the Ecdysone receptors (EcR)-B1 or EcR-B2 isoform of the ecdysone receptor-B (EcR-B) following a surge in the steroid hormone at the beginning of pupariation [54]. This binding occurs redundantly in astrocyte-like or cortex glial cells [56] causing the secretion of the ligand Myoglianin (Myo), which binds to the Babo-A receptor in vCrz neurons, activating TGF-β signaling and leading to apoptosis [55]

  • Astro-like or cortex glial cells at the receptor to growth. It binds to either Astro-like or cortex glial cells at the EcR-B receptor to trigger the trigger the production of Myo, which binds to the Babo-A receptor in vCrz neurons causing apoptosis via TGF-β signaling

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Summary

Systemic Growth Inhibition by DL-Crz Modulation of Ecdysone

Systemic growth is regulated by 20-hydroxyecdysone during development, hereby referred to as ecdysone, which is the active form of a steroid hormone secreted by the prothoracic gland and has been implicated in a myriad of powerful and diverse signaling pathways [37,38]. Basal levels of ecdysone have been shown to negatively control system body growth by acting as an antagonist to general insulin signaling via interaction with the fat body, a structure homologous to the liver in vertebrates [39]. This relationship was further validated when silencing of Ecdysone receptors (EcR) resulted in increased pupal size [39]. Anatomical and functional analyses demonstrate that DL-Crz cells activate CrzR expressed in PTTH neurons [17]. The pharyngeal input is consistent with the role of Crz neurons in modulating systemic growth, while the input from T1–T3 interneurons with. CO2 information is consistent with the many roles of Crz regarding stress described elsewhere in the paper

Ecdysone-Driven Apoptosis of vCrz Neurons during Metamorphosis
Developmental
Ethanol Recovery and Consumption Are Regulated by Crz Neuron Function
Crz Functions as a Hub Regulating Ejaculation within the VNC
Crz-Independent Function of abgCrz Neurons
Activation of Crz Neurons Is Pleasurable
Future Directions
Findings
Conclusions
Full Text
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