Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings.
Bringing to light the physiological and pathological firing patterns of human induced pluripotent stem cell-derived neurons using optical recordings.
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DOI：
10.3389/fncel.2022.1039957
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发表时间：
2022
影响因子：
5.3
通讯作者：
中科院分区：
文献类型：
--
作者：
人类诱导多能干细胞（hiPSC）是研究神经系统和神经精神疾病的一种有前途的方法。大多数记录这些细胞活性的方法都有很大的缺点，因为它们是侵入性的，或者它们不允许单细胞分辨率。遗传编码电压指示器（GEVI）开辟了未受干扰的神经元活动的高通量可视化的道路。然而，常规GEVI通过将跨膜结构域的多个拷贝插入质膜中来扰乱膜完整性。为了避免质膜上的大量附加物，我们使用了一种微创的新型混合暗淬灭剂GEVI来记录来自遗传性红斑性肢痛症患者的hiPSC衍生的感觉神经元的生理和病理放电模式，遗传性红斑性肢痛症是一种与远端四肢反复发作的红肿相关的慢性疼痛病症。我们观察到病人和对照组神经元之间的动作电位放电模式有相当大的差异，这在以前的记录方法中被忽视了。我们的系统在hiPSC衍生的前脑神经元中也表现良好，在那里它检测到自发的同步爆发行为，从而为未来在其他细胞类型和疾病模型中的应用开辟了道路，包括帕金森病，阿尔茨海默病，癫痫和精神分裂症，与神经元活动和同步性紊乱相关的病症。
Human induced pluripotent stem cells (hiPSCs) are a promising approach to study neurological and neuropsychiatric diseases. Most methods to record the activity of these cells have major drawbacks as they are invasive or they do not allow single cell resolution. Genetically encoded voltage indicators (GEVIs) open the path to high throughput visualization of undisturbed neuronal activity. However, conventional GEVIs perturb membrane integrity through inserting multiple copies of transmembrane domains into the plasma membrane. To circumvent large add-ons to the plasma membrane, we used a minimally invasive novel hybrid dark quencher GEVI to record the physiological and pathological firing patterns of hiPSCs-derived sensory neurons from patients with inherited erythromelalgia, a chronic pain condition associated with recurrent attacks of redness and swelling in the distal extremities. We observed considerable differences in action potential firing patterns between patient and control neurons that were previously overlooked with other recording methods. Our system also performed well in hiPSC-derived forebrain neurons where it detected spontaneous synchronous bursting behavior, thus opening the path to future applications in other cell types and disease models including Parkinson’s disease, Alzheimer’s disease, epilepsy, and schizophrenia, conditions associated with disturbances of neuronal activity and synchrony.
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影响因子：
3.7
作者：
Imbrici P;Camerino DC;Tricarico D
通讯作者：
Tricarico D
影响因子：
3.4
作者：
Akemann, Walther;Lundby, Alicia;Knopfel, Thomas
通讯作者：
Knopfel, Thomas
影响因子：
3
作者：
Hill, M. R. H.;Greenfield, S. A.
通讯作者：
Greenfield, S. A.
影响因子：
5.7
作者：
Elanzew A;Nießing B;Langendoerfer D;Rippel O;Piotrowski T;Schenk F;Kulik M;Peitz M;Breitkreuz Y;Jung S;Wanek P;Stappert L;Schmitt RH;Haupt S;Zenke M;König N;Brüstle O
通讯作者：
Brüstle O
影响因子：
--
作者：
DALTON, JC;HENDRIX, DE
通讯作者：
HENDRIX, DE