生物化学セミナー（Abdelhalim Azzi 2014/3/31）
演者： Abdelhalim 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 andphysiology 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 SCNnetwork 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
nsight into the mechanisms underlying this form of circadian plasticity.
世話人：深田 吉孝（内線24381）
