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Journal of Traditional Chinese Medicine >

2026 , Vol. 46 >Issue 3: 552 - 560

DOI: https://doi.org/10.19852/j.cnki.jtcm.2026.03.003

Original Articles

Role of gamma-aminobutyric acid-ergic neurons in the thalamic reticular nucleus in regulating sleep-wake cycles in mice treated with acupuncture for insomnia

  • LU Xiaoxiao ,
  • XU Yipeng ,
  • ZHOU Minjie ,
  • ZHANG Chengshun ,
  • CAI Dingjun ,
  • ZHAO Zhengyu
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  • 1 Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
    2 Department of acupuncture and moxibustion, First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China
    3 Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
First author contact:

LU Xiaoxiao and XU Yipeng are co-first authors and contributed equally to this work

ZHAO Zhengyu, CAI Dingjun, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China. zhaozhengyu@cdutcm.edu.cn;
CAI Dingjun, Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China. djcai@cdutcm.edu.cn, Telephone: +86-28-61703327

Received date: 2025-02-12

  Accepted date: 2025-07-22

  Online published: 2026-06-08

Supported by

National Natural Science Foundation of China: Mechanism Study on the Cholinergic-gamma-aminobutyric acid-ergic Neural Regulatory Effect of the Thalamic Reticular Nucleus in Acupuncture Regulating Sleep-Wake disturbance(81774434);Circadian-Controlled Microglia-Neuron Interactions Mechanism within the Thalamic Reticular Nucleus Underlying Acupuncture Amelioration of Insomnia-Induced Attention Deficits(82274659);Sichuan Province Science and Technology Program: Study on the Exosome-Mediated Mast Cell-Neural Modulation Mechanism Underlying Acupoint Sensitization(2019YJ0330);Circadian-Controlled Neuro-Immune Regulation Mechanism of Chrono-Acupuncture for Neuropathic Pain via SP-Mrgprb2R Pathway(2021YJ0177);Chengdu University of Traditional Chinese Medicine Foundation Program: Acupuncture Modulates Thalamic Reticular Nucleus Microglia-Neuronal Crosstalk in Sleep Disorder-Induced Attention Deficits(QJJJ2021005)

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Abstract

OBJECTIVE: To test whether acupuncture improves sleep by enhancing gamma-aminobutyric acid-ergic (GABA) neuronal activity in the thalamic reticular nucleus (TRN).

METHODS: We established an animal model using p-chlorophenylalanine (PCPA). We assessed the impact of acupuncture on insomnia through wheel-running activity and sodium pentobarbital-induced sleep tests. Subsequently, the calcium indicator GCaMP6m was injected into the TRN of Vgat-Cre mice, and the activity of GABA neurons in the TRN was analyzed before and after acupuncture using fiber photometry recording. Additionally, cortical electroencephalography (EEG) recordings were compared between groups following chemogenetic inhibition of GABA neurons in the TRN.

RESULTS: Following acupuncture, we observed a reduction in sleep latency and an increase in sleep duration in comparison to the PCPA-induced insomnia (P < 0.01). Furthermore, acupuncture positively influenced the diurnal phase of insomnia (P < 0.01). Ca2+ signals in GABA neurons within the TRN increased post-acupuncture (paired t-test, P< 0.01). Acupuncture also reduced the proportion of EEG power in the elevated Beta and Gamma frequencies associated with PCPA injection, while simultaneously increasing the Delta power ratio (P < 0.01). Chemogenetic inhibition of TRN GABA neurons blocked these acupuncture effects: the hM4Di + MA group showed no significant differences from the PCPA group in Beta and Gamma power, but exhibited elevated Beta and Theta activity compared to controls (P < 0.05).

CONCLUSIONS: Acupuncture activates GABA neurons in the TRN, thereby regulating the sleep-wake cycle in the context of PCPA-induced insomnia.

Key words： acupuncture; insomnia disorder; sleep; wake; thalamic reticular nucleus; gamma-aminobutyric acid-ergic neurons

Cite this article

LU Xiaoxiao , XU Yipeng , ZHOU Minjie , ZHANG Chengshun , CAI Dingjun , ZHAO Zhengyu . Role of gamma-aminobutyric acid-ergic neurons in the thalamic reticular nucleus in regulating sleep-wake cycles in mice treated with acupuncture for insomnia[J]. Journal of Traditional Chinese Medicine, 2026 , 46(3) : 552 -560 . DOI: 10.19852/j.cnki.jtcm.2026.03.003

References

1. Dopheide JA. Insomnia overview: epidemiology, pathophysiology, diagnosis and monitoring, and nonpharmacologic therapy. Am J Manag Care 2020; 26: S76-84.
2. Stranges S, Tigbe W, Gómez-Olivé FX, et al. Sleep problems: an emerging global epidemic? Findings from the INDEPTH WHO-SAGE study among more than 40 000 older adults from 8 countries across Africa and Asia. Sleep 2012; 35: 1173-81.
3. Wilt TJ, MacDonald R, Brasure M, et al. Pharmacologic treatment of insomnia disorder: an evidence report for a clinical practice guideline by the American college of physicians. Ann Intern Med 2016; 165: 103-12.
4. Yin X, Gou M, Xu J, et al. Efficacy and safety of acupuncture treatment on primary insomnia: a randomized controlled trial. Sleep Med 2017; 37: 193-200.
5. Yin X, Li W, Liang T, et al. Effect of electroacupuncture on insomnia in patients with depression: a randomized clinical trial. JAMA Netw Open 2022; 5: e2220563.
6. Tang L, You F, Hu X, et al. Electroacupuncture improves insomnia by down-regulating peripheral benzodiazepine receptor expression in hippocampus, and up-regulating 5-HT, 5-HIAA, TNF-α and IL-1β contents in hypothalamus in insomnia rats. Zhen Ci Yan Jiu 2019; 44: 560-65.
7. Zhou YL, Gao XY, Wang PY, et al. Effect of acupuncture at different acupoints on expression of hypothalamic GABA and GABA(A) receptor proteins in insomnia rats. Zhen Ci Yan Jiu 2012; 37: 302-7.
8. Jing MY, Liu JN, Cai DJ, et al. Effects of electroacupuncture on the prokineticin 2 receptor of the dorsomedial hypothalamus and lateral hypothalymus area in the rats due to advanced light/dark cycle. Shi Zhen Guo Yi Guo Yao 2019; 30: 744-7.
9. Okamura H, Abitbol M, Julien JF, et al. Neurons containing messenger RNA encoding glutamate decarboxylase in rat hypothalamus demonstrated by in situ hybridization, with special emphasis on cell groups in medial preoptic area, anterior hypothalamic area and dorsomedial hypothalamic nucleus. Neuroscience 1990; 39: 675-99.
10. Jin W, Kim MS, Jang EY, et al. Acupuncture reduces relapse to cocaine-seeking behavior via activation of GABA neurons in the ventral tegmental area. Addict Biol 2018; 23: 165-81.
11. Li Z, Chen J, Cheng J, et al. Acupuncture modulates the cerebello-thalamo-cortical circuit and cognitive brain regions in patients of parkinson's disease with tremor. Front Aging Neurosci 2018; 10: 206.
12. Murase T, Umeda M, Higuchi T. Investigation of acupuncture-specific BOLD signal changes using multiband acquisition and deconvolution analysis. Magn Reson Med Sci 2021; 20: 425-30.
13. Ferrarelli F, Tononi G. The thalamic reticular nucleus and schizophrenia. Schizophr Bull 2011; 37: 306-15.
14. Ni KM, Hou XJ, Yang CH, et al. Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep. Elife 2016; 5:10382.
15. Jagirdar R, Fu CH, Park J, et al. Restoring activity in the thalamic reticular nucleus improves sleep architecture and reduces Aβ accumulation in mice. Sci Transl Med 2021; 13: eabh4284.
16. Sun H, Shen S, Thomas RJ, et al. Sleep as a window to understand and regulate Alzheimer's disease: emerging roles of thalamic reticular nucleus. Neural Regen Res 2025; 20: 1711-12.
17. Zhang Y, Cheng SZ, Hua Y, et al. Mechanisms of Suanzaoren (Ziziphi Spinosae Semen) and its processed products in treating insomnia: an integrated study based on network pharmacology and metabolomics. J Tradit Chin Med 2025; 45: 1307-16.
18. Thankachan S, Katsuki F, McKenna JT, et al. Thalamic reticular nucleus parvalbumin neurons regulate sleep spindles and electrophysiological aspects of schizophrenia in mice. Sci Rep 2019; 9: 3607.
19. Dib R, Gervais NJ, Mongrain V. A review of the current state of knowledge on sex differences in sleep and circadian phenotypes in rodents. Neurobiol Sleep Circadian Rhythms 2021; 11: 100068.
20. Yu KC, Wei HT, Chang SC, et al. The efficacy of combined electroacupuncture and auricular pressure on sleep quality in patients receiving methadone maintenance treatment. Am J Addict 2021; 30: 156-63.
21. Yeni K, Tulek Z, Terzi M. Effect of self-acupressure on fatigue in patients with multiple sclerosis. Complement Ther Clin 2022; 47: 101572.
22. Lee KC, Chao YC, Lin YP, et al. Effectiveness of self-administered acupressure for family caregivers of advanced cancer patients with insomnia: a randomized controlled trial. Cancer Nurs 2022; 45: E1-9.
23. Yi PL, Lu CY, Cheng CH, et al. Activation of amygdala opioid receptors by electroacupuncture of Feng-Chi (GB20) acupoints exacerbates focal epilepsy. BMC Complement Altern Med 2013; 13: 290.
24. Li A, Li R, Ouyang P, et al. Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia. Cns Neurosci Ther 2021; 27: 941-50.
25. Kim S, Jo K, Hong KB, et al. GABA and l-theanine mixture decreases sleep latency and improves NREM sleep. Pharm Biol 2019; 57: 65-73.
26. Qiu G, Wu Y, Yang Z, et al. Dexmedetomidine activation of dopamine neurons in the ventral tegmental area attenuates the depth of sedation in mice. Anesthesiology 2020; 133: 377-92.
27. Zhang H, He W, Hu XF, et al. Electroacupuncture reduces visceral pain via cannabinoid CB2 receptors in a mouse model of inflammatory bowel disease. Front Pharmacol 2022; 13: 861799.
28. Yang H, Lee YC, Han KS, et al. Green and gold kiwifruit peel ethanol extracts potentiate pentobarbital-induced sleep in mice via a GABAergic mechanism. Food Chem 2013; 136: 160-3.
29. Welsh D, Richardson GS, Dement WC. Effect of running wheel availability on circadian patterns of sleep and wakefulness in mice. Physiol Behav 1988; 43: 771-7.
30. Wang J, Lu FF, Ge MM, et al. Transcutaneous electrical acupoint stimulation improves postoperative sleep quality in patients undergoing laparoscopic gastrointestinal tumor surgery: a prospective, randomized controlled trial. Pain Ther 2023; 12: 707-22.
31. Liu CH, Liu CZ, Zhang J, et al. Reduced spontaneous neuronal activity in the insular cortex and thalamus in healthy adults with insomnia symptoms. Brain Res 2016; 1648: 317-24.
32. Wu WZ, Zheng SY, Liu CY, et al. Effect of Tongdu Tiaoshen acupuncture on serum GABA and CORT levels in patients with chronic insomnia. Zhong Guo Zhen Jiu 2021; 41: 721-4.
33. Zhang F, Zhang X, Peng Q, et al. Electroacupuncture of the cymba concha alleviates p-chlorophenylalanine-induced insomnia in mice. Acupunct Med 2023; 41: 345-53.
34. Gardner RJ, Hughes SW, Jones MW. Differential spike timing and phase dynamics of reticular thalamic and prefrontal cortical neuronal populations during sleep spindles. J Neurosci 2013; 33: 18469-80.
35. Perlis ML, Smith MT, Andrews PJ, et al. Beta/gamma EEG activity in patients with primary and secondary insomnia and good sleeper controls. Sleep 2001; 24: 110-7.
36. Revel FG, Gottowik J, Gatti S, et al. Rodent models of insomnia: a review of experimental procedures that induce sleep disturbances. Neurosci Biobehav Rev 2009; 33: 874-99.
37. Yi G, Wang J, Bian H, et al. Multi-scale order recurrence quantification analysis of EEG signals evoked by manual acupuncture in healthy subjects. Cogn Neurodyn 2013; 7: 79-88.
38. Kim MS, Kim HD, Seo HD, et al. The effect of acupuncture at PC-6 on the electroencephalogram and electrocardiogram. Am J Chin Med 2008; 36: 481-91.
39. Rowe DL, Robinson PA, Lazzaro IL, et al. Biophysical modeling of tonic cortical electrical activity in attention deficit hyperactivity disorder. Int J Neurosci 2005; 115: 1273-305.
40. Rahimi S, Soleymankhani A, Joyce L, et al. Discriminating rapid eye movement sleep from wakefulness by analyzing high frequencies from single-channel EEG recordings in mice. Sci Rep 2023; 13: 9608.
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