Coupling Neuropeptide Levels to Structural Plasticity in Drosophila Clock Neurons

Curr Biol. 2020 Aug 17;30(16):3154-3166.e4. doi: 10.1016/j.cub.2020.06.009. Epub 2020 Jul 2.


We have previously reported that pigment dispersing factor (PDF) neurons, which are essential in the control of rest-activity cycles in Drosophila, undergo circadian remodeling of their axonal projections, a phenomenon called circadian structural plasticity. Axonal arborizations display higher complexity during the day and become simpler at night, and this remodeling involves changes in the degree of connectivity. This phenomenon depends on the clock present within the ventrolateral neurons (LNvs) as well as in glia. In this work, we characterize in detail the contribution of the PDF neuropeptide to structural plasticity at different times across the day. Using diverse genetic strategies to temporally restrict its downregulation, we demonstrate that even subtle alterations to PDF cycling at the dorsal protocerebrum correlate with impaired remodeling, underscoring its relevance for the characteristic morning spread; PDF released from the small LNvs (sLNvs) and the large LNvs (lLNvs) contribute to the process. Moreover, forced depolarization recruits activity-dependent mechanisms to mediate growth only at night, overcoming the restriction imposed by the clock on membrane excitability. Interestingly, the active process of terminal remodeling requires PDF receptor (PDFR) signaling acting locally through the cyclic-nucleotide-gated channel ion channel subunit A (CNGA). Thus, clock-dependent PDF signaling shapes the connectivity of these essential clock neurons on daily basis.

Keywords: CNGA; LNvs; PDF; activity-dependent synaptic plasticity; circadian remodeling; lLNvs; sLNvs; structural plasticity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Circadian Clocks*
  • Circadian Rhythm
  • Cyclic Nucleotide-Gated Cation Channels / genetics
  • Cyclic Nucleotide-Gated Cation Channels / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism*
  • Motor Activity
  • Neuronal Plasticity*
  • Neurons / cytology
  • Neurons / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism


  • Calcium Channels
  • CngA protein, Drosophila
  • Cyclic Nucleotide-Gated Cation Channels
  • Drosophila Proteins
  • Neuropeptides
  • PDFR protein, Drosophila
  • Receptors, G-Protein-Coupled