Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (2): 425-433.doi: 10.4103/1673-5374.379048

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Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

Feng Chen1, 2, #, Xi Dong1, 3, #, Zhenhuan Wang1, Tongrui Wu1, Liangpeng Wei1, 4, Yuanyuan Li5, Kai Zhang6, Zengguang Ma1, #br# Chao Tian1, Jing Li7, Jingyu Zhao1, Wei Zhang8, *, Aili Liu9, *, Hui Shen5, 9, * #br#   

  1. 1Laboratory of Neurobiology, School of Biomedical Engineering, Tianjin Medical University, Tianjin, China; 2Institute for Translational Neuroscience, the Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China; 3Institute for Translational Brain Research, Fudan University, Shanghai, China; 4Department of Radiology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China; 5Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China; 6Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China; 7Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, China; 8Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin, China; 9Laboratory of Neurobiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
  • Online:2024-02-15 Published:2023-08-30
  • Contact: Hui Shen, MD, PhD, shenhui@tmu.edu.cn; Aili Liu, MS, liuaili6201@tmu.edu.cn; Wei Zhang, MD, PhD, zhangwei3067@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 62027812 (to HS), 81771470 (to HS), and 82101608 (to YL); Tianjin Postgraduate Research and Innovation Project, No. 2020YJSS122 (to XD).

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Abstract: Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory, resistant to antiepileptic drugs, and has a high recurrence rate. The pathogenesis of temporal lobe epilepsy is complex and is not fully understood. Intracellular calcium dynamics have been implicated in temporal lobe epilepsy. However, the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown, and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice. In this study, we used a multi-channel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process. We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes. In particular, cortical spreading depression, which has recently been frequently used to represent the continuously and substantially increased calcium signals, was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from grade II to grade V. However, vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures. Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to grade I episodes. In addition, the latency of cortical spreading depression was prolonged, and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced. Intriguingly, it was possible to rescue the altered intracellular calcium dynamics. Via simultaneous analysis of calcium signals and epileptic behaviors, we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced, and that the end-point behaviors of temporal lobe epilepsy were improved. Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades. Furthermore, the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy, thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Key words: Ca2+, calcium signals, chemogenetic methods, hippocampus, primary motor cortex, pyramidal neurons, temporal lobe epilepsy