- 學位論文
果蠅腦中調控溫度喜好之神經網路於⽼化過程中的變化
Parallel circuits control temperature preference in Drosophila during aging
摘要
感測環境溫度是人類與其他動物與生俱來的的能力。微觀生物體內各種生理反應所需的酵素，對環境溫度的變化相當敏感。因此，生物體必須尋找最有利的環境溫度，幫助體內各種維持新陳代謝的化學反應能順利進行。然而，溫度調控的能力隨著年齡增長而逐漸失去效率。在我們的研究當中，發現年老的果蠅對於低溫的躲避性降低，顯示個體對冷的敏感度隨著年齡而下降。除了觀察到這個現象外，我們更找到大腦中控制該行為變化的神經結構—蕈狀體(Mushroom Body)和分子作用機制。果蠅腦中兩個獨立的神經網絡MB β′ 和 MB β分別在個體老化的過程中，各自透過神經傳導物質-多巴胺分泌量的改變，共同調控果蠅對低溫的躲避性。MB β′ 在年輕果蠅的溫度偏好行為中扮演主要角色。然而，隨著果蠅老化過程中，MB β的重要性逐漸超越MB β′的角色，主導年老果蠅溫度喜好的行為表現。過去研究發現，許多生物在低溫環境下，代謝速率降低，導致身體產生的自由基減少，暗示著處於低溫環境對延緩老化可能是一個有利的抉擇。而我們的發現，正好提供一個方向，用以解釋老化過程中，生物體對溫度喜好改變的生理意義。
並列摘要
The detection of environmental temperature and regulation of body temperatures are integral determinants of behavior for all animals. These functions seemingly become less efficient in aged animals, especially during exposure to cold environments. We reasoned that a clearer understanding of the underlying molecular and cellular mechanisms that alter set point temperatures during aging could reveal insights into why such age-related changes occur. Here, we identified an age-related change in the temperature preference of adult fruit flies, which results from a shift in the relative contributions of two parallel mushroom body (MB) circuits—the β′ and β systems. The β′ circuit primarily controls cold avoidance through dopamine signaling in young flies, whereas the β circuit increasingly contributes to cold avoidance as adult flies age. The restoration of cold sensitivity in aged flies by elevating dopamine levels in β′ afferent neurons suggests that the alteration of cold avoidance behavior with aging is functionally reversible. These findings add to the diverse functions of the MB subregions and provide a framework to investigate how molecules and neural circuits modulate homeostatic alterations during the course of senescence.