Fiber photometry-based analysis of transcranial magneto-acoustic electrical stimulation effects on synaptic plasticity in the hippocampal CA1 region of APP/PS1 mice_Journal of Biomedical Engineering

Authors：

MI Jinrui ^1,2,3 ,  ZHANG Shuai ^1,2,3 , LU Xiaochao ^1,2,3 , XU Yihao ^1,2,3 , XU Guizhi ^1,2,3

1. School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin 300130, P. R. China;
2. State Key Laboratory of Intelligent Power Distribution Equipment and System, Hebei University of Technology, Tianjin 300130, P. R. China;
3. Hebei Key Laboratory of Bioelectromagnetics and Neuroengineering, Hebei University of Technology, Tianjin 300130, P. R. China;

Corresponding?author：

ZHANG Shuai, Email: zs@hebut.edu.cn

Keywords：

Transcranial magneto-acoustic electrical stimulation; Synaptic plasticity; Hippocampal CA1 region; Calcium activity; APP/PS1 mice

DOI：

10.7507/1001-5515.202503076

Video：

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Transcranial magneto-acoustic electrical stimulation (TMAES) is a non-invasive novel neuromodulation technique based on the magneto-acoustic coupling effect. In this study, we employed APP/PS1 transgenic mice as an experimental model, targeting the hippocampus. Cognitive function was assessed through behavioral tests, while neuronal morphology was examined using hematoxylin-eosin and Golgi staining. Additionally, fiber photometry was utilized to measure calcium transient intensity in the CA1 region. By investigating the effects of TMAES on synaptic plasticity in the hippocampus, we aimed to elucidate its potential regulatory mechanisms in improving cognitive function in AD mice. Behavioral results showed that the cognitive and memory abilities of mice in the AD+sham group were significantly lower than those in the WT+sham group, while TMAES intervention could significantly improve the cognitive function of mice in the AD+TMAES group. Morphological detection indicated that the number of pyramidal neurons and the density of dendritic spines in the hippocampal CA1 region of the AD+sham group were decreased, with an increased proportion of immature spines; all the above indicators were significantly improved after TMAES intervention. Fiber photometric detection revealed that the calcium activity and calcium amplitude of neurons in the CA1 region of the AD+TMAES group were significantly enhanced compared with those of the AD+sham group. Pearson correlation analysis showed that cognitive level was positively correlated with calcium amplitude, dendritic spine density, and mature spine proportion. Meanwhile, calcium amplitude was positively correlated with dendritic spine density and mature spine proportion. Therefore, TMAES may alleviate the damage to synaptic plasticity in the hippocampal CA1 region of APP/PS1 mice by regulating the function of calcium ion channels, thereby improving cognitive impairment.

Citation： MI Jinrui, ZHANG Shuai, LU Xiaochao, XU Yihao, XU Guizhi. Fiber photometry-based analysis of transcranial magneto-acoustic electrical stimulation effects on synaptic plasticity in the hippocampal CA1 region of APP/PS1 mice. Journal of Biomedical Engineering, 2026, 43(1): 8-16. doi: 10.7507/1001-5515.202503076 Copy

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24.	Zhou X, Liu S, Wang Y, et al. High-resolution transcranial electrical simulation for living mice based on magneto-acoustic effect. Front Neurosci, 2019, 13: 1342.
25.	Zhang S, Xie X, Xu Y, et al. Effects of transcranial magneto-acoustic stimulation on cognitive function and neural signal transmission in the hippocampal CA1 region of mice. Neuroscience, 2024, 556: 86-95.
26.	Chu F, Tan R, Wang X, et al. Transcranial magneto-acoustic stimulation attenuates synaptic plasticity impairment through the activation of Piezo1 in Alzheimer’s disease mouse model. Research, 2023, 6: 0130.
27.	張帥, 武健康, 許家悅, 等. 經顱磁聲電刺激對前額葉皮層神經集群鈣信號的影響. 生物醫學工程學雜志, 2022, 39(1): 19-27.
28.	Chen T W, Wardill T J, Sun Y, et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature, 2013, 499(7458): 295-300.
29.	Dong X, Zhang X, Wang F, et al. Simultaneous calcium recordings of hippocampal CA1 and primary motor cortex M1 and their relations to behavioral activities in freely moving epileptic mice. Exp Brain Res, 2020, 238(6): 1479-1488.
30.	Mehder R H, Bennett B M, Andrew R D. Morphometric analysis of hippocampal and neocortical pyramidal neurons in a mouse model of late onset Alzheimer’s disease. J Alzheimers Dis, 2020, 74(4): 1069-1083.
31.	Tan X, Ma H, Guo X, et al. Disinhibition of hippocampal parvalbumin interneurons on pyramidal neurons participates in LPS-induced cognitive dysfunction. Neurosci Lett, 2024, 821: 137614.
32.	Miller M R, Lee Y F, Kastanenka K V. Calcium sensor yellow cameleon 3. 6 as a tool to support the calcium hypothesis of Alzheimer’s disease. Alzheimer Dement, 2023, 19(9): 4196-4203.
33.	Guo M, Zhang F, Liu S, et al. The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption. Cell Insight, 2025, 4(3): 100240.

1. Koch G, Altomare D, Benussi A, et al. The emerging field of non-invasive brain stimulation in Alzheimer’s disease. Brain, 2024, 147(12): 4003-4016.
2. Weller J, Budson A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Res, 2018, 7: F1000 Faculty Rev-1161.
3. 2024 Alzheimer’s disease facts and figures. Alzheimers Dement, 2024, 20(5): 3708-3821.
4. Busche M A, Konnerth A. Impairments of neural circuit function in Alzheimer’s disease. Philos Trans R Soc Lond B Biol Sci, 2016, 371(1700): 20150429.
5. Frere S, Slutsky I. Alzheimer’s disease: From firing instability to homeostasis network collapse. Neuron, 2018, 97(1): 32-58.
6. Rolls E T, Wirth S. Spatial representations in the primate hippocampus, and their functions in memory and navigation. Prog Neurobiol, 2018, 171: 90-113.
7. Horovitz D J, Askins L A, Regnier G M, et al. Age-related synaptic signatures of brain and cognitive reserve in the rat hippocampus and parahippocampal regions. Neurobiol Aging, 2025, 148: 80-97.
8. Neuman K M, Molina-Campos E, Musial T F, et al. Evidence for Alzheimer's disease-linked synapse loss and compensation in mouse and human hippocampal CA1 pyramidal neurons. Brain Struct Funct, 2015, 220(6): 3143-3165.
9. Bouwman M M A, Frigerio I, Reijner N, et al. Synaptic density in the hippocampal and parahippocampal subregions and its association with the severity of axonal damage and cognitive decline in Alzheimer’s disease. Alzheimers Dement, 2024, 20: e092170.
10. Forner S, Kawauchi S, Balderrama-Gutierrez G, et al. Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer’s disease. Sci Data, 2021, 8(1): 270.
11. Ebrahimi R, Golzari Z, Heidari-Foroozan M, et al. Impaired synaptic plasticity mechanisms in Alzheimer’s disease. Metab Brain Dis, 2025, 40(7): 277.
12. Button E B, Boyce G K, Wilkinson A, et al. ApoA-I deficiency increases cortical amyloid deposition, cerebral amyloid angiopathy, cortical and hippocampal astrogliosis, and amyloid-associated astrocyte reactivity in APP/PS1 mice. Alzheimers Res Ther, 2019, 11(1): 44.
13. Pchitskaya E, Popugaeva E, Bezprozvanny I. Calcium signaling and molecular mechanisms underlying neurodegenerative diseases. Cell Calcium, 2018, 70: 87-94.
14. Sushma, Mondal A C. Role of GPCR signaling and calcium dysregulation in Alzheimer’s disease. Mol Cell Neurosci, 2019, 101: 103414.
15. Venkateswaran N, Karthik S, Raghavan S, et al. A temporal analysis of long term synaptic plasticity. Int J Dev Neurosci, 2006, 24(8): 549-550.
16. Ji Y, Yang C, Pang X, et al. Repetitive transcranial magnetic stimulation in Alzheimer’s disease: Effects on neural and synaptic rehabilitation. Neural Regen Res, 2025, 20(2): 326-342.
17. Bast T, Pezze M, McGarrity S. Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition. Br J Pharmacol, 2017, 174(19): 3211-3225.
18. Harris S S, Wolf F, De Strooper B, et al. Tipping the scales: peptide-dependent dysregulation of neural circuit dynamics in Alzheimer’s disease. Neuron, 2020, 107(3): 417-435.
19. Selkoe D J. Alzheimer’s disease is a synaptic failure. Science, 2002, 298(5594): 789-791.
20. Choung J S, Kim J M, Ko M H, et al. Therapeutic efficacy of repetitive transcranial magnetic stimulation in an animal model of Alzheimer’s disease. Sci Rep, 2021, 11(1): 437.
21. Matt E, Mitterwallner M, Radjenovic S, et al. Ultrasound neuromodulation with transcranial pulse stimulation in Alzheimer disease: A randomized clinical trial. JAMA Netw Open, 2025, 8(2): e2459170.
22. Zhang S, Guo Z, Xu Y, et al. Transcranial magneto-acoustic stimulation improves spatial memory and modulates hippocampal neural oscillations in a mouse model of Alzheimer’s disease. Front Neurosci, 2024, 18: 1313639.
23. Mi J, Zhang S, Lu X, et al. Transcranial magneto-acoustic stimulation enhances cognitive and working memory in AD rats by regulating theta-gamma oscillation coupling and synergistic activity in the hippocampal CA3 region. Brain Sci, 2025, 15(7): 701.
24. Zhou X, Liu S, Wang Y, et al. High-resolution transcranial electrical simulation for living mice based on magneto-acoustic effect. Front Neurosci, 2019, 13: 1342.
25. Zhang S, Xie X, Xu Y, et al. Effects of transcranial magneto-acoustic stimulation on cognitive function and neural signal transmission in the hippocampal CA1 region of mice. Neuroscience, 2024, 556: 86-95.
26. Chu F, Tan R, Wang X, et al. Transcranial magneto-acoustic stimulation attenuates synaptic plasticity impairment through the activation of Piezo1 in Alzheimer’s disease mouse model. Research, 2023, 6: 0130.
27. 張帥, 武健康, 許家悅, 等. 經顱磁聲電刺激對前額葉皮層神經集群鈣信號的影響. 生物醫學工程學雜志, 2022, 39(1): 19-27.
28. Chen T W, Wardill T J, Sun Y, et al. Ultrasensitive fluorescent proteins for imaging neuronal activity. Nature, 2013, 499(7458): 295-300.
29. Dong X, Zhang X, Wang F, et al. Simultaneous calcium recordings of hippocampal CA1 and primary motor cortex M1 and their relations to behavioral activities in freely moving epileptic mice. Exp Brain Res, 2020, 238(6): 1479-1488.
30. Mehder R H, Bennett B M, Andrew R D. Morphometric analysis of hippocampal and neocortical pyramidal neurons in a mouse model of late onset Alzheimer’s disease. J Alzheimers Dis, 2020, 74(4): 1069-1083.
31. Tan X, Ma H, Guo X, et al. Disinhibition of hippocampal parvalbumin interneurons on pyramidal neurons participates in LPS-induced cognitive dysfunction. Neurosci Lett, 2024, 821: 137614.
32. Miller M R, Lee Y F, Kastanenka K V. Calcium sensor yellow cameleon 3. 6 as a tool to support the calcium hypothesis of Alzheimer’s disease. Alzheimer Dement, 2023, 19(9): 4196-4203.
33. Guo M, Zhang F, Liu S, et al. The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption. Cell Insight, 2025, 4(3): 100240.

Journal of Biomedical Engineering

Fiber photometry-based analysis of transcranial magneto-acoustic electrical stimulation effects on synaptic plasticity in the hippocampal CA1 region of APP/PS1 mice

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