清大生醫學院系神所江安世教授

Professor Ann-Shyn Chiang of the Institute of Systems Neuroscience, College of Life Sciences and Medicine, National Tsing Hua University.

論文標題Paper Title

Thirst-driven hygrosensory suppression promotes water seeking in Drosophila

學術期刊刊名Journal Name

美國國家科學院院刊Proc Natl Acad Sci U S A

研究團隊 Research Team

主持人Principle Investigator：

朱麗安 副教授Li- An Chu, Associate Professor

國立清華大學生命科學暨醫學院 系統神經科學研究所

Institute of Systems Neuroscience, National Tsing Hua University (NTHU).

參與者Participants:：

戴竹儀  研究員

國立清華大學腦科學研究中心

Chu- Yi Tai, Brain Research Center, NTHU

江安世 教授  

國立清華大學生命科學暨醫學院 系統神經科學研究所

Ann-Shyn Chiang,  Professor, Institute of Systems Neuroscience, National Tsing Hua University (NTHU).

摘要

Abstract

果蠅具備精細的濕度感知能力，對其生存至關重要。清華大學研究團隊發現，果蠅天線上的小囊結構內有三類神經元：IR40a感知乾燥、IR68a感知濕潤、IR8a在不缺水時驅動濕潤回避行為。當果蠅缺水時，神經肽Leucokinin (Lk)會抑制IR8a的活性，使果蠅轉而吸引濕潤環境。透過RNA干擾與光遺傳學等技術，研究人員證實這些神經元協作調控果蠅的濕度選擇行為，幫助其在不同環境中生存。此研究揭示了昆蟲在環境壓力下精確調節行為的神經機制，為理解動物內外感知調控提供新啟示。

Survival in animals relies on navigating environments aligned with physiological needs. In Drosophila melanogaster, antennal ionotropic receptors (IRs) sensing humidity changes govern hygrotaxis behavior. This study sheds light on the crucial role of IR8a neurons in the transition from high humidity avoidance to water-seeking behavior when the flies become thirsty. These neurons demonstrate a heightened calcium response toward high humidity stimuli in satiated flies and a reduced response in thirsty flies, modulated by fluctuating levels of the neuropeptide leucokinin, which monitors the internal water balance. Optogenetic activation of IR8a neurons in thirsty flies triggers an avoidance response similar to the moisture aversion in adequately hydrated flies. Furthermore, our study identifies IR40a neurons as associated with dry avoidance, while IR68a neurons are linked to moist attraction. The dynamic interplay among these neurons, each with opposing valences, establishes a preference for approximately 30% relative humidity in well-hydrated flies and facilitates water-seeking behavior in thirsty individuals. This research unveils the intricate interplay between sensory perception, neuronal plasticity, and internal states, providing valuable insights into the adaptive mechanisms governing hygrotaxis in Drosophila.

研究成果Result/Contributions

在黑腹果蠅(Drosophila melanogaster)中，對環境濕度的偏好會根據體內水分狀態動態改變。當果蠅水分充足時，偏好約 30% 相對濕度(RH)的環境，會主動避開過於潮濕的區域；而當果蠅處於缺水狀態，尤其脫水達 3 小時後，則轉而偏好較高濕度 (約 70% RH)的環境。這種行為上的轉變由不同的濕度感知神經元所調控：IR40a 神經元促進對乾燥空氣的迴避、IR68a 神經元吸引果蠅靠近濕潤空氣，而本研究新發現的 IR8a 神經元則在水分充足時驅動果蠅對高濕度環境的迴避。

透過 RNA 介導的基因表現抑制與 T 形迷宮行為實驗，研究人員發現 IR8a 神經元對於維持水分充足狀態下的濕度偏好至關重要。當 IR8a 表現被抑制時，果蠅不再表現對 30% RH 的偏好，顯示其在「濕潤迴避行為」中扮演關鍵角色。鈣影像顯示：在水分充足的果蠅中，IR8a神經元對濕度刺激表現出高活性；但在缺水狀態下，這些反應會顯著下降。相比之下，IR68a 神經元在兩種狀態下皆對濕度呈正向反應，且在缺水情況下感受更為敏感。

光遺傳學實驗進一步證實：在水分充足的果蠅中，刺激 IR8a 神經元會誘發對濕潤環境的迴避反應；但在缺水果蠅中，此迴避行為會因神經肽 leucokinin (Lk)的抑制作用而消失。該神經肽會因體內滲透壓升高而分泌，進而抑制 IR8a 的活性。施加 Lk 神經肽可模擬此抑制效果；而阻斷 IR8a 神經元上的 Lk 受體，則能使缺水果蠅重新表現出濕潤迴避行為。

整體而言，IR8a 神經元是果蠅濕度偏好行為的關鍵開關：在水分充足時處於活化狀態並產生迴避行為；在缺水時則被 Lk 抑制，使果蠅能主動尋找水源。本研究提出一個整合外部濕度與內部生理狀態的三神經元模型：IR40a(乾燥迴避)、IR68a(濕潤吸引)、IR8a(濕潤迴避)，揭示果蠅如何透過神經機制實現適應性水分行為調控。

In Drosophila melanogaster, humidity preference dynamically shifts depending on hydration state. Satiated flies prefer environments with ~30% relative humidity (RH), avoiding overly moist areas, while thirsty flies increasingly prefer higher humidity (~70% RH), especially after 3 hours of dehydration. This behavioral switch is mediated by distinct hygrosensory neurons: IR40a neurons promote avoidance of dry air, IR68a neurons attract flies to moist air, and IR8a neurons—newly identified in this study—drive avoidance of high humidity when flies are well-hydrated.

Through RNAi screening and behavioral assays using a humidity-controlled T-maze, the researchers discovered that IR8a neurons are crucial for maintaining humidity preference in hydrated flies. Downregulating IR8a expression eliminated the preference for 30% RH, indicating its role in moist-avoidance behavior. Calcium imaging revealed that IR8a neurons show high activation in response to humidity in hydrated flies, but this response is significantly suppressed in thirsty flies. In contrast, IR68a neurons consistently respond positively to humidity, with enhanced sensitivity in dehydrated conditions.

Optogenetic activation experiments confirmed that IR8a neuron stimulation elicits avoidance behavior in hydrated flies, regardless of actual humidity levels. However, in thirsty flies, this moist-avoidance behavior is suppressed due to inhibition of IR8a neurons by the neuropeptide leucokinin (Lk), which is released in response to internal osmolarity changes. Application of Lk peptide mimicked this inhibition, while blocking Lk receptors in IR8a neurons restored avoidance behavior, even in thirsty flies.

Together, these findings reveal that IR8a neurons function as a dynamic behavioral switch: they are active and aversive under normal hydration, but are suppressed under dehydration to allow for water-seeking behavior. The study establishes a three-neuron model: IR40a (dry avoidance), IR68a (moist attraction), and IR8a (moist avoidance when hydrated), integrating external humidity cues with internal thirst states to produce adaptive behavior in Drosophila.

論文連結 Paper Link

https://www.pnas.org/doi/epub/10.1073/pnas.2404454121