Tac1-KO Mouse

Tac1, also known as tachykinin 1, encodes a transcription factor in Candida albicans and is a key player in regulating drug resistance [1]. In mammals, it is expressed in specific neurons and is involved in various neural-related functions such as itch-scratching cycles, defensive responses, sexual behavior, social interactions, and mood-related behaviors [2-6, 8-10]. These functions are associated with multiple neural pathways in the body.

In mouse models, ablation or suppression of Tac1-expressing neurons in the lateral and ventrolateral periaqueductal gray (l/vlPAG) decreased itch-induced scratching behavior, indicating their role in promoting the itch-scratching cycle [2]. In the context of toxin-induced defensive responses, the gut-to-brain circuit transmits signals to Tac1+ neurons in the dorsal vagal complex (DVC), which drive retching-like behavior and conditioned flavor avoidance [3]. Manipulating circuits related to Tac1+ DVC neurons also interferes with defensive responses induced by chemotherapeutic drugs. In male sexual behavior, a neural circuit connecting chemosensory input to BNSTprTac1 neurons, which innervate POATacr1 neurons, is necessary and sufficient for male mating [4]. In social interactions, activation of PVH-projecting Tac1+ neurons in the l/vlPAG promotes social interactions [5]. Selective inhibition and activation of Tac1-expressing neurons in the nucleus accumbens (NAc) lateral shell bidirectionally modulate stress susceptibility, regulating anhedonia-like behaviors [6]. Also, NAcTac1 neurons in the NAc medial shell regulate avoidance responses to aversive stimuli [7].

In conclusion, Tac1 is crucial for multiple biological functions, especially in neural-mediated processes. Studies using mouse models, such as those with manipulation of Tac1-expressing neurons, have revealed its significant contributions to processes like itch-scratching, defensive responses, sexual behavior, social interactions, and mood-related behaviors. These findings help in understanding the underlying mechanisms of related diseases and neural dysfunctions [2-4, 6, 8, 9].

References:

1. Mahdizade, Amir Hossein, Hoseinnejad, Akbar, Ghazanfari, Mona, Haghani, Iman, Romeo, Orazio. 2024. The TAC1 Gene in Candida albicans: Structure, Function, and Role in Azole Resistance: A Mini-Review. In Microbial drug resistance (Larchmont, N.Y.), 30, 288-296. doi:10.1089/mdr.2023.0334. https://pubmed.ncbi.nlm.nih.gov/38770776/

2. Gao, Zheng-Run, Chen, Wen-Zhen, Liu, Ming-Zhe, Xu, Xiao-Hong, Sun, Yan-Gang. 2018. Tac1-Expressing Neurons in the Periaqueductal Gray Facilitate the Itch-Scratching Cycle via Descending Regulation. In Neuron, 101, 45-59.e9. doi:10.1016/j.neuron.2018.11.010. https://pubmed.ncbi.nlm.nih.gov/30554781/

3. Xie, Zhiyong, Zhang, Xianying, Zhao, Miao, Shang, Congping, Cao, Peng. 2022. The gut-to-brain axis for toxin-induced defensive responses. In Cell, 185, 4298-4316.e21. doi:10.1016/j.cell.2022.10.001. https://pubmed.ncbi.nlm.nih.gov/36323317/

4. Bayless, Daniel W, Davis, Chung-Ha O, Yang, Renzhi, Luo, Liqun, Shah, Nirao M. 2023. A neural circuit for male sexual behavior and reward. In Cell, 186, 3862-3881.e28. doi:10.1016/j.cell.2023.07.021. https://pubmed.ncbi.nlm.nih.gov/37572660/

5. Yu, Hang, Miao, Wanying, Ji, En, Xu, Fuqiang, Yu, Xiang. 2022. Social touch-like tactile stimulation activates a tachykinin 1-oxytocin pathway to promote social interactions. In Neuron, 110, 1051-1067.e7. doi:10.1016/j.neuron.2021.12.022. https://pubmed.ncbi.nlm.nih.gov/35045339/

6. He, Zi-Xuan, Yin, Yue-Yue, Xi, Ke, Yu, Hua-Li, Zhu, Xiao-Juan. . Nucleus Accumbens Tac1-Expressing Neurons Mediate Stress-Induced Anhedonia-like Behavior in Mice. In Cell reports, 33, 108343. doi:10.1016/j.celrep.2020.108343. https://pubmed.ncbi.nlm.nih.gov/33147466/

7. He, Zi-Xuan, Xi, Ke, Liu, Kai-Jie, Xing, Zhen-Kai, Zhu, Xiao-Juan. 2023. A Nucleus Accumbens Tac1 Neural Circuit Regulates Avoidance Responses to Aversive Stimuli. In International journal of molecular sciences, 24, . doi:10.3390/ijms24054346. https://pubmed.ncbi.nlm.nih.gov/36901777/