東京大学 大学院理学系研究科 生物化専攻セミナー
演者：Dr. Adbelhalim Azzi
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
演題：Day length reorganizes the SCN neuronal network
日時：平成26年3月31日（月）16：00〜17：30
場所：東京大学理学部3号館3階303号室

In mammals, daily behavior and physiology are controlled by the suprachiasmatic nuclei (SCN) of the hypothalamus (Master clock). The period lengths of these processes are partially controlled by genetic factors. However, previous studies have also shown that exposing genetically identical mice to light/dark cycles longer or shorter than 24 hours can result in long-lasting changes of endogenous free-running period (FRP) (“aftereffects”, Pittendrigh 1976). These changes in period, is referred to period “aftereffects” and can persist for months in constant conditions. We have shown that such aftereffects are dependent upon dynamic DNA methylation in the SCN (Azzi et al., Nat. Neurosci, 2014).
To understand the mechanistic underpinning of period aftereffects, 3-week-old PER2::LUC mice were entrained to non-24h light: dark cycles (T-cycles) of 22, 24 or 26 hours. As expected, behavioral period aftereffects were proportional to T-cycle length (22.5, 24, and 25 hours respectively). Also consistent with previous work (Aton 2004; Molyneux 2008), but far less easily explained, SCN period lengths in vitro recorded from T cycle-entrained mice displayed a negative correlation with behavioral period. Therefore, we hypothesized that non-24h light:dark cycles may change SCN network properties by altering intercellular coupling. Surprisingly, bioluminescence imaging revealed that SCN spatiotemporal organization is markedly affected by T-cycle length, with complete reversal of the phase relationship between dorsal and ventral SCN. Supporting the idea that interneuronal coupling plays an important role in aftereffects, period of SCN slices from mice with both long- and short-period aftereffects could be normalized to 23.5 hours by treatment with Tetrodotoxin (TTX), which blocks neuronal network. Importantly, we find that GABAergique signaling, which is involved in SCN interregional coupling, plays a crucial role in aftereffects. Period of SCN slices from mice with both long- and short-period aftereffects could be relaxed after treatment with GABA blocker.
These results indicate that entrainment to non-24h light dark cycle likely alters SCN organization through changes in network properties. Further experiments should provide insight into the mechanisms underlying this form of circadian plasticity.

世話人：理学系研究科　深田 吉孝