GABA-mediated repulsive coupling between circadian clock neurons in the SCN encodes seasonal time

Jihwan Myung, Sungho Hong, Daniel DeWoskin, Erik De Schutter, Daniel B. Forger, Toru Takumi

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The mammalian suprachiasmatic nucleus (SCN) forms not only the master circadian clock but also a seasonal clock. This neural network of ∼10,000 circadian oscillators encodes season-dependent day-length changes through a largely unknown mechanism. We show that region-intrinsic changes in the SCN fine-tune the degree of network synchrony and reorganize the phase relationship among circadian oscillators to represent day length. We measure oscillations of the clock gene Bmal1, at single-cell and regional levels in cultured SCN explanted from animals raised under short or long days. Coupling estimation using the Kuramoto framework reveals that the network has couplings that can be both phase-attractive (synchronizing) and -repulsive (desynchronizing). The phase gap between the dorsal and ventral regions increases and the overall period of the SCN shortens with longer day length. We find that one of the underlying physiological mechanisms is the modulation of the intracellular chloride concentration, which can adjust the strength and polarity of the ionotropic GABAA-mediated synaptic input. We show that increasing daylength changes the pattern of chloride transporter expression, yielding more excitatory GABA synaptic input, and that blocking GABAA signaling or the chloride transporter disrupts the unique phase and period organization induced by the day length. We test the consequences of this tunable GABA coupling in the context of excitation-inhibition balance through detailed realistic modeling. These results indicate that the network encoding of seasonal time is controlled by modulation of intracellular chloride, which determines the phase relationship among and period difference between the dorsal and ventral SCN.

Original languageEnglish
Pages (from-to)E3920-E3929
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number29
DOIs
Publication statusPublished - Jul 21 2015
Externally publishedYes

Keywords

  • Chloride
  • Day-length encoding
  • GABA
  • Repulsive coupling
  • SCN

ASJC Scopus subject areas

  • General

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