Tac1, also known as tachykinin 1 or transcriptional activator candidate 1, has diverse functions. In Candida albicans, it encodes a transcription factor regulating drug resistance genes like efflux pump genes (CDR1, CDR2, MDR1) and ERG11, with mutations conferring azole resistance [1,6]. In mammals, it is involved in neural circuits related to various behaviors. Tac1 -expressing neurons in different brain regions are associated with behaviors such as the itch-scratching cycle, toxin-induced defensive responses, male sexual behavior, stress-induced anhedonia, social interactions, and avoidance of aversive stimuli, as well as odor-driven innate fear and anxiety [2,3,4,5,7,8,9].

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 gut-to-brain axis study, manipulating the circuit involving Tac1+ neurons in the dorsal vagal complex (DVC) interfered with toxin-induced defensive responses [3]. In the study of male sexual behavior, epistasis studies on a neural circuit including BNSTprTac1 neurons demonstrated their upstream role in initiating mating [4]. In the context of anhedonia-like behavior, selective inhibition and activation of Tac1-expressing neurons in the nucleus accumbens lateral shell bidirectionally modulated stress susceptibility [5].

In conclusion, Tac1 is crucial in multiple biological processes and disease-related behaviors. Mouse models with manipulated Tac1-expressing neurons have revealed its roles in behaviors related to itch, toxin response, sexual behavior, anhedonia, social interactions, aversion, and fear. Understanding Tac1 may provide insights into the mechanisms of these behaviors and potential therapeutic targets for related disorders.

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/

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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. 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/

6. Czajka, Karolina M, Venkataraman, Krishnan, Brabant-Kirwan, Danielle, Saunders, Deborah P, Tharmalingam, Sujeenthar. 2023. Molecular Mechanisms Associated with Antifungal Resistance in Pathogenic Candida Species. In Cells, 12, . doi:10.3390/cells12222655. https://pubmed.ncbi.nlm.nih.gov/37998390/

7. 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/

8. 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/

9. Wang, Hao, Wang, Qin, Cui, Liuzhe, Cao, Peng, Li, Xiao-Ming. 2024. A molecularly defined amygdala-independent tetra-synaptic forebrain-to-hindbrain pathway for odor-driven innate fear and anxiety. In Nature neuroscience, 27, 514-526. doi:10.1038/s41593-023-01562-7. https://pubmed.ncbi.nlm.nih.gov/38347199/