A TTX-sensitive local circuit is involved in the expression of PK2 and BDNF circadian rhythms in the mouse suprachiasmatic nucleus

The roles of a local circuit of electrophysiological activity were examined in the expression of circadian rhythms in the suprachiasmatic nucleus (SCN) of the adult mouse. The neuronal activity of cultured SCN was suppressed with tetrodotoxin (TTX), an Na+ channel blocker, and the circadian rhythms in mRNA level were assessed for 13 genes by in situ hybridization. SCN slices were cultured for 3 days and TTX was applied at the peak phase of Per1 expression rhythm. The SCN slices were examined at 4-h intervals up to 32 h after TTX application. The circadian rhythms in the expression of clock genes, Per1, Per2, Bmal1 and Cry1, and of clock-associated genes, Dec1, Dec2, Rev-erb alpha, Rev-erb beta and DBP, were not affected by TTX treatment. By contrast, TTX completely abolished the circadian rhythm in the BDNF mRNA level and substantially damped the rhythm in PK2. The circadian rhythm in the AVP mRNA level was not changed significantly by TTX. These findings indicate that input through Na+-channel-dependent electrophysiological activity is not necessary for the expression of the circadian rhythms of clock and clock-associated genes, but necessary for full expression of the circadian rhythms of BDNF and PK2 in the SCN. A TTX-sensitive circuit is involved in the expression of BDNF and PK2 circadian rhythms in the mouse SCN.