Mystery of rhythmic signal emergence within the suprachiasmatic nuclei.

The circadian system provides organisms with a temporal organization that optimizes their adaptation to environmental fluctuations on a 24-hr basis. In mammals, the circadian clock in the suprachiasmatic nuclei (SCN) develops during the perinatal period. The rhythmicity first appears at the level of individual SCN neurons during the fetal stage, and this step is often misinterpreted as the time of complete SCN clock development. However, the process is only finalized when the SCN begin to play a role of the central clock in the body, that is, when they are able to generate robust rhythmicity at the cell population level, entrain the rhythmic signal with external light-dark cycles and convey this signal to the rest of the body. The development is gradual and correlates with morphological maturation of the SCN structural complexity, which is based on intercellular network formation. The aim of this review is to summarize events related to the first emergence of circadian oscillations in the fetal SCN clock. Although a large amount of data on ontogenesis of the circadian system have been accumulated, how exactly the immature SCN converts into a functional central clock has still remained rather elusive. In this review, the hypothesis of how the SCN attains its rhythmicity at the tissue level is discussed in context with the recent advances in the field. For an extensive summary of the complete ontogenetic development of the circadian system, the readers are referred to other previously published reviews.