Our lab studies how animals sense their environment, integrate past experience and internal states, and use this information to make behavioral decisions. Using Caenorhabditis elegans as our primary model, we investigate the neural and molecular mechanisms underlying sensory processing, behavioral states, learning and plasticity, sexually dimorphic behaviors, and interactions between the nervous system and microbiota. Our research combines genetics and molecular biology with quantitative behavioral analysis, optogenetics, calcium imaging, microfluidics, automated tracking, and machine-learning-based behavioral classification. By integrating these approaches across molecular, cellular, circuit, and behavioral levels, we aim to understand how nervous systems transform sensory information into flexible and persistent behaviors.
Interdisciplinary across genetics/molecular biology/imaging/behavioral analysis
Mate recognition is crucial to exchange genetic variations to maintain phenotypic plasticity during evolution. Precise recognition of suitable mates is mediated through sensory perceptions to recognize conspecific and reproductive mates. With the computation of sensory stimuli, animals then decide behavioral outputs to select suitable mates. Our current study has shown that C. elegans males can recognize suitable mates through physical contact (Weng et al., 2023) and change behavioral states to increase the chance to mate with hermaphrodites. Apart from the decision-making, we notice that the alteration of behavioral states is sustained without further stimuli representing a fundamental element of cognitive functions. We then study the neural mechanisms of decision-making and persistency of behavioral state. Starting with the simple nervous system in C. elegans, which only has 302 neurons in hermaphrodites, we anticipate that these studies of decision-making and persistence of behavioral changes in mate recognition can help us understand the brain functions in complex organisms.
動物間的身體接觸在動物界的社交行為中至關重要。以交配行爲來說,動物必須尋覓合適的對象,透過伴侶辨識的社交行為完成辨識及交配。一般來說,動物依賴化學因子作為遠距離溝通的訊息來找到適合伴侶,當距離靠近時,則使用不同的物理性因子來解讀作為近距離的訊號。透過化學性及物理性的感官訊號,生物可以精準且有效的解讀伴侶的資訊。過去研究大量著重於交配識別的化學訊號,但對於哪些物理性因子可以做為感官訊號並不完全暸解。
我們發現了秀麗隱桿線蟲中會透過兩段式的辨認機制來辨識潛在伴侶。首先,角質層上未知的因子會觸發交配識別初始步驟。接著,需要倚賴特定的身體硬度來維持伴侶的吸引力,最終完成整個伴侶辨識的行爲,並增加交配的成功率。實驗成果因此說明了身體硬度可以做為物理性感覺訊號,並在動物社交行為中扮演著重要角色。(Weng et al., 2023. Current Biology)
Across animal species, males and females differ not only in their appearance but also in the structure and function of their nervous systems. These differences shape how each sex perceives the environment, makes behavioral decisions, and engages in social interactions. Yet, a fundamental question remains: how does biological sex influence neural development? Are these differences encoded by intrinsic genetic programs within each cell, or are they molded by signals from neighboring cells and the surrounding environment?By combining genetics, live imaging, and multi-omic approaches, we investigate how sex-determining signals interact with cytoskeletal dynamics, chaperonin-mediated protein folding, and tissue-derived cues to sculpt sexually specific neuronal architectures. Our research not only provides a mechanistic understanding of how sex shapes the nervous system but also offers new insights into the origins of sex-biased neurological disorders in humans.
在多數動物中,雄性與雌性不僅外觀不同,連神經系統的結構與功能也各具特色。這些差異使牠們在感知環境、做出行為決策與社交互動時呈現出明顯的性別特徵。然而,「性別」究竟如何影響神經發育?是基因在細胞內部直接決定,還是來自外部環境與鄰近細胞的信號所塑造?這些問題在哺乳類中難以區分,因為性荷爾蒙會在早期發育階段全面影響全身組織。
我們的實驗室以線蟲 Caenorhabditis elegans 為模型,利用其可精準操控的性別決定系統,研究神經元如何在不同性別環境中發育與分化。線蟲的雄性與雌雄同體擁有相似的神經網路,但部分神經元在分支、突觸連結與感覺反應上展現出明顯差異。我們結合遺傳學、活體成像與多體學分析,揭示性別信號如何與細胞骨架、蛋白摺疊系統及外部組織訊號互動,最終塑造出性別特異的神經結構 (Yang et al., 2025)。這些研究不僅幫助我們理解性別在神經系統中的基礎作用,也為探討人類神經發育障礙與性別差異相關疾病提供了新的線索。
Although the decision-making of animals’ behaviors has drawn much attention in neuroscience, the genes and cellular mechanisms controlling decision-making have not been satisfyingly understood. The main difficulty is that the mechanistic details are not sufficiently revealed at a single cell level due to the limit of tools in animal models. We found that C. elegans males are able to recognize suitable mates through physical contact, and we want to study the underlying neural mechanisms. By using a novel cGAL-UAS system, the Chen lab disseminate the neural mechanisms of decision-making of mate recognition in C. elegans.
在神經科學領域裡,如何透過神經訊號傳遞而做出決定,是一個重要且複雜的問題,雖然科學家努力尋找其中的奧妙,但我們對於要如何做決定的神經機制以及在細胞及分子階層發生的事情,並不是完全暸解。最主要的問題是,在大多數的多細胞模式生物中,很難建立一個有效的系統,研究一個神經細胞在決定時中產生的變化,像是神經訊號的強度改變或是蛋白的產生。我們發現雄性線蟲可以有效率的透過物理性接觸辨認不同的交配對象,這讓我們開始想研究哪些神經細胞及分子機制參與在伴侶辨識中。在實驗室裡,我們利用線蟲中已經建立的cGAL-UAS系統性基因表達的基因轉殖線蟲,將可以大量且有系統的研究其中所參與的神經細胞以及其功能。
High cognitive functions such as emotions require persistency of behavioral states in high order organisms, where sensory perceptions or behavioral outputs are altered for a certain period to meet the environmental stimuli and internal state. For example, the chance you get candies from parents is different, likely higher when they are happy. It is a reversible change of neural states as the loss of potential stimuli is accompanied by the fade of the neural states. This persistent state efficiently shortens the response time for future stimuli; however, the genetic and neural mechanisms remain unclear. Our preliminary data found that males drastically change their locomotion patterns after brief contact with hermaphrodites, and this change will sustain for at least 5 minutes. We will use advanced genetics and technology to tackle this question for the persistency of neural states in C. elegans.
對於高階的動物體,認知功能會受到不同神經狀態下而被影響,像是我們會在不同情緒下,對於相同的感官訊息而做出不同反應,例如:在父母生氣或開心時,要糖果吃的成功率是不一樣的。而這種感官功能的變化,會持續一段時間,並在外界刺激消失後逐漸褪去。這種行為的持續性,將會有效率的縮短生物體對於外在環境的反應時間。一個有趣的問題是生物如何讓自己在接受刺激後進入持續性的行為,這也伴隨著這些持續性行為如何逐漸消散。因此,我們實驗室想要研究這些問題,在我們初步的實驗中已經發現,雄性線蟲短暫碰觸雌雄同體時會改變其行為模式,而這種行為改變會維持至少數分鐘,並回覆到先前的狀態。我們對於這種神經調控機制相當感興趣,實驗室將會利用遺傳學與新穎的神經學研究方式,去研究在線蟲行為中持續狀態的神經機制。