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Tetrodotoxin resets the clock.

Takako Noguchi1, Kazuto Watanabe

  • 1Department of Physiology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.

The European Journal of Neuroscience
|July 20, 2005
PubMed
Summary
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Disrupting neuronal firing in the suprachiasmatic nucleus (SCN) with tetrodotoxin (TTX) or NMDA alters circadian rhythms. These findings reveal how SCN neuronal activity influences the mammalian internal clock.

Area of Science:

  • Neuroscience
  • Chronobiology

Background:

  • Circadian rhythms in mammals are regulated by the suprachiasmatic nucleus (SCN) in the hypothalamus.
  • Arginine vasopressin release is a key marker of SCN pacemaker activity.

Purpose of the Study:

  • To investigate the effects of inhibiting or exciting SCN neurons on circadian rhythm phase.
  • To compare the phase-resetting effects of tetrodotoxin (TTX) and N-methyl-D-aspartate (NMDA) on the SCN clock.

Main Methods:

  • Organotypic SCN slices from rats were used to measure arginine vasopressin release.
  • Application of TTX (neuronal blocker) or NMDA (excitatory neurotransmitter) at different circadian times (CT).

Main Results:

  • TTX application induced phase advances when applied in the mid-subjective day (CT 7.0) and phase delays when applied in the early subjective morning (CT 2.0), mimicking dark pulse effects.

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  • NMDA application induced phase delays in the early evening and phase advances in the late night, similar to light pulse effects.
  • Deprivation of neuronal firing significantly alters the circadian rhythm.

    • Conclusions:

    • Neuronal activity within the SCN is crucial for maintaining and regulating circadian timing.
    • Differential responses to TTX and NMDA suggest distinct mechanisms by which neuronal firing influences circadian phase.
    • These findings provide insights into the molecular and cellular basis of the mammalian circadian clock.