視交叉上核編碼空間上的訊息來調節光同步生理時鐘

Abstract

哺乳動物位於下視丘的視交叉上核(SCN)，會產生約 24 小時節律的指令並影響生理功能像是睡眠清醒週期，並同步各部位的周邊時鐘，所以被視為是生理時鐘的中央節律點。眼睛內視網膜的自主感光視網膜神經節細胞(ipRGCs)可以將外界的光訊息傳遞到視交叉上核，調節晝夜節律的同步，又稱作光同步生理時鐘(circadian photoentrainment)。而過去行為實驗的結果顯示，晝夜節律的相移(phase shift)程度會受到2個因子影響：接受到的光子數量和內生性生理時間。然而，自主感光視網膜神經節細胞和視交叉上核之間的神經連結以及光同步生理時鐘的機制目前仍未知。根據目前的研究，視交叉上核的腹外側(ventrolateral part)是主要接受來自自主感光視神經細胞所傳遞光線訊息的區域。有趣的是，最近的研究顯示自主感光視網膜神經節細胞也可以直接投射到視交叉上核的背側(dorsal part)。利用不同方向的光線和 c-Fos 免疫螢光染色，我們發現視交叉上核的背側和腹側的神經細胞可以分別不同方向的光線活化，且在相同亮度的情況下，不同方向的光線可以引發不同程度的相移。總結來說，視交叉上核內不同區域的神經細胞可以被來自不同方向的光線活化，進而影響晝夜節律的同步。

In mammals, the central circadian pacemaker suprachiasmatic nucleus (SCN) in the hypothalamus plays an important role to synchronize the peripheral clocks in a roughly 24-hour cycle and influence many physiological functions such as sleep-wake cycle. In addition, the SCN receives retinal inputs from the photoreceptors, intrinsically photosensitive retinal ganglion cells (ipRGCs), to mediate circadian photoentrainment. Behavioral tests indicated that circadian phase-shift response is determined by two factors: number of photons and circadian time. However, the neural connection from ipRGCs to the SCN remain poorly understood. Previous studies suggested that the ventrolateral SCN is the primary recipient region of photic input. Intriguingly, recent studies showed that the dorsal SCN may receive synaptic inputs from ipRGCs directly despite the physiological function is still unclear. Using different direction of light and c-Fos staining, here we showed that ipRGCs may activate the dorsal and ventral SCN differentially. Surprisingly, the phase shifts display significant differences with our different direction of light under the same illuminance. These results indicate the possibility that direction of light may be an effective factor to determine circadian phase response.