REVIEW ARTICLE Clock mechanisms for seasonal adaptation: Morning and evening oscillators in the suprachiasmatic nucleus Sato HONMA, 1,2 Natsuko INAGAKI, 1 Daisuke ONO, 1 Tomoko YOSHIKAWA, 2 Satoko HASHIMOTO 1,2 and Ken-ichi HONMA 1 1 Department of Physiology, and 2 Department of Chronomedicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Abstract The circadian behavioral rhythms show seasonal changes not only in animals in the field but also in humans in urban environments. In nocturnal rodents the activity time is compressed or decom- pressed in response to day lengths. A two-oscillator model has been proposed to explain this photoperiodic response; an evening (E) oscillator is entrained to a dusk signal and drives activity onset, while a morning (M) oscillator is entrained to a dawn signal and controls the end of the active period. However, the location and the oscillation mechanism for these oscillators remain to be elucidated. Recent progress in understanding molecular circadian clock mechanisms and biolumi- nescent reporters for clock gene expressions enabled us to monitor the E and M clocks’ tick separately. We measured clock gene Per1 expression levels continuously from individual cells as well as tissue explants of the hypothalamic suprachiasmatic nucleus (SCN) using transgenic mice carrying a luciferase reporter gene (Per1-luc mice) which were kept in different photoperiods. We found that there are two regionally specific oscillatory cell groups in the SCN that regulate activity onset and end separately in response to photoperiods, which we assume correspond to E and M oscillators. In addition, a third group of oscillatory cells was identified in the SCN only in a long photoperiod. These oscillatory cell networks change dynamically their clock gene expression pattern depending on environmental lights. Similar mechanisms may underlie seasonal changes in sleep time and mela- tonin rhythms of humans. Key words: behavior, clock gene, luciferase reporter, multioscillator pacemaker, photoperiod, suprachiasmatic nucleus. INTRODUCTION Adaptation to seasonal changes in environment is criti- cal for the survival of many organisms living in the middle and high latitudes. Animals prepare for seasonal changes such as the cold winter with reduced food availability and a harsh environment by collecting foods, increasing their body fat, decreasing their energy expen- diture, growing a thick winter coat, preparing safe shel- ters, migrating to warmer places and/or hibernating. The mechanism by which animals know the time of year remains an enigma. Free-running of circannual rhythms have been reported in several animals, which eviden- tially supports the view that at least some animals, such as migrating birds and seasonally breeding sheep, have circannual clocks. 1,2 Another mechanism that animals have evolved for knowing the seasons is to measure day length, in other words, the photoperiodic time measure- ment, by the circadian clock. Although the photoperi- odic changes have been extensively studied in the Correspondence: Dr. Sato Honma, Departments of Physiology and Chronomedicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. Email: sathonma@med.hokudai.ac.jp Accepted for publication 16 March 2008. Sleep and Biological Rhythms 2008; 6: 84–90 doi:10.1111/j.1479-8425.2008.00347.x 84 © 2008 The Authors Journal compilation © 2008 Japanese Society of Sleep Research