GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons

Sara J. Aton, James E. Huettner, Martin Straume, Erik D. Herzog

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

Neurons in the mammalian suprachiasmatic nuclei (SCN) generate daily rhythms in physiology and behavior, but it is unclear how they maintain and synchronize these rhythms in vivo. We hypothesized that parallel signaling pathways in the SCN are required to synchronize rhythms in these neurons for coherent output. We recorded firing and clock-gene expression patterns while blocking candidate signaling pathways for at least 8 days. GABAA and GABAB antagonism increased circadian peak firing rates and rhythm precision of cultured SCN neurons, but Gi/o did not impair synchrony or rhythmicity. In contrast, inhibiting Gi/o with pertussis toxin abolished rhythms in most neurons and desynchronized the population, phenocopying the loss of vasoactive intestinal polypeptide (VIP). Daily VIP receptor agonist treatment restored synchrony and rhythmicity to VIP -/- SCN cultures during continuous GABA receptor antagonism but not during Gi/o blockade. Pertussis toxin did not affect circadian cycling of the liver, suggesting that Gi/o plays a specialized role in maintaining SCN rhythmicity. We conclude that endogenous GABA controls the amplitude of SCN neuronal rhythms by reducing daytime firing, whereas Gi/o signaling suppresses nighttime firing, and it is necessary for synchrony among SCN neurons. We propose that Gi/o, not GABA activity, converges with VIP signaling to maintain and coordinate rhythms among SCN neurons.

Original languageEnglish
Pages (from-to)19188-19193
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number50
DOIs
StatePublished - Dec 12 2006

Keywords

  • Luciferase
  • Multielectrode array
  • Period gene
  • Suprachiasmatic nucleus
  • Vasoactive intestinal polypeptide

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