Functional Peptidomics: Stimulus- and Time-of-Day-Specific Peptide Release in the Mammalian Circadian Clock

Norman Atkins, Shifang Ren, Nathan Hatcher, Penny W. Burgoon, Jennifer W. Mitchell, Jonathan V. Sweedler, Martha U. Gillette

Research output: Contribution to journalArticle

Abstract

Daily oscillations of brain and body states are under complex temporal modulation by environmental light and the hypothalamic suprachiasmatic nucleus (SCN), the master circadian clock. To better understand mediators of differential temporal modulation, we characterize neuropeptide releasate profiles by nonselective capture of secreted neuropeptides in an optic nerve horizontal SCN brain slice model. Releasates are collected following electrophysiological stimulation of the optic nerve/retinohypothalamic tract under conditions that alter the phase of the SCN activity state. Secreted neuropeptides are identified by intact mass via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found time-of-day-specific suites of peptides released downstream of optic nerve stimulation. Peptide release was modified differentially with respect to time-of-day by stimulus parameters and by inhibitors of glutamatergic or PACAPergic neurotransmission. The results suggest that SCN physiology is modulated by differential peptide release of both known and unexpected peptides that communicate time-of-day-specific photic signals via previously unreported neuropeptide signatures.

Original languageEnglish (US)
Pages (from-to)2001-2008
Number of pages8
JournalACS Chemical Neuroscience
Volume9
Issue number8
DOIs
StatePublished - Aug 15 2018

Keywords

  • Circadian clock
  • SCN
  • mass spectrometry
  • neuropeptidomics
  • optic nerve
  • suprachiasmatic nucleus

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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