关键词: axons excitation inhibition morphology organotypic tissue cultures synaptic plasticity whole-cell patch-clamp recordings

来  源:   DOI:10.3389/fncel.2024.1374555   PDF(Pubmed)

Abstract:
UNASSIGNED: Repetitive transcranial magnetic stimulation (rTMS) is a widely used therapeutic tool in neurology and psychiatry, but its cellular and molecular mechanisms are not fully understood. Standardizing stimulus parameters, specifically electric field strength, is crucial in experimental and clinical settings. It enables meaningful comparisons across studies and facilitates the translation of findings into clinical practice. However, the impact of biophysical properties inherent to the stimulated neurons and networks on the outcome of rTMS protocols remains not well understood. Consequently, achieving standardization of biological effects across different brain regions and subjects poses a significant challenge.
UNASSIGNED: This study compared the effects of 10 Hz repetitive magnetic stimulation (rMS) in entorhino-hippocampal tissue cultures from mice and rats, providing insights into the impact of the same stimulation protocol on similar neuronal networks under standardized conditions.
UNASSIGNED: We observed the previously described plastic changes in excitatory and inhibitory synaptic strength of CA1 pyramidal neurons in both mouse and rat tissue cultures, but a higher stimulation intensity was required for the induction of rMS-induced synaptic plasticity in rat tissue cultures. Through systematic comparison of neuronal structural and functional properties and computational modeling, we found that morphological parameters of CA1 pyramidal neurons alone are insufficient to explain the observed differences between the groups. Although morphologies of mouse and rat CA1 neurons showed no significant differences, simulations confirmed that axon morphologies significantly influence individual cell activation thresholds. Notably, differences in intrinsic cellular properties were sufficient to account for the 10% higher intensity required for the induction of synaptic plasticity in the rat tissue cultures.
UNASSIGNED: These findings demonstrate the critical importance of axon morphology and intrinsic cellular properties in predicting the plasticity effects of rTMS, carrying valuable implications for the development of computer models aimed at predicting and standardizing the biological effects of rTMS.
摘要:
重复经颅磁刺激(rTMS)是神经病学和精神病学中广泛使用的治疗工具,但其细胞和分子机制尚未完全了解。标准化刺激参数,特别是电场强度,在实验和临床环境中至关重要。它可以在研究中进行有意义的比较,并有助于将研究结果转化为临床实践。然而,受刺激的神经元和网络固有的生物物理特性对rTMS协议结果的影响仍未得到很好的理解。因此,实现跨不同大脑区域和受试者的生物效应标准化提出了重大挑战。
这项研究比较了10Hz重复磁刺激(rMS)对小鼠和大鼠海马组织培养物的影响,提供在标准化条件下相同刺激协议对类似神经元网络的影响的见解。
我们观察到先前描述的小鼠和大鼠组织培养中CA1锥体神经元的兴奋性和抑制性突触强度的可塑性变化,但是在大鼠组织培养物中诱导rMS诱导的突触可塑性需要更高的刺激强度。通过神经元结构和功能特性的系统比较和计算模型,我们发现仅CA1锥体细胞的形态参数不足以解释观察到的组间差异.尽管小鼠和大鼠CA1神经元的形态没有显着差异,模拟证实轴突形态显著影响单个细胞活化阈值。值得注意的是,固有细胞特性的差异足以解释在大鼠组织培养物中诱导突触可塑性所需的10%的高强度。
这些发现证明了轴突形态和内在细胞特性在预测rTMS的可塑性效应中的关键重要性,对旨在预测和标准化rTMS生物学效应的计算机模型的开发具有重要意义。
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