The suprachiasmatic nuclei contain a tetrodotoxin-resistant circadian pacemaker

Tetrodotoxin was infused into the suprachiasmatic nuclei of unanesthetized and unrestrained rats continuously for 14 days. The internal timekeeping mechanism of the circadian pacemaker in the nuclei continued to oscillate unaffected by this treatment, although the toxin reversibly blocked function of both the input pathway for pacemaker entrainment and an output pathway for expression of the circadian drinking rhythm. Thus, Na+-dependent action potentials appear necessary for entrainment and expression of overt circadian rhythms, but they do not seem necessary for the pacemaker to keep accurate time. The experimental approach presented in this paper is useful because it allows systematic assessment and distinction of the input, pacemaker, and output components of a mammalian circadian timekeeping system in vivo.