Synapses without tension fail to fire in an in vitro network of hippocampal neurons
Synapses without tension fail to fire in an in vitro network of hippocampal neurons
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DOI：
10.1073/pnas.2311995120
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发表时间：
2023-12-26
影响因子：
11.1
通讯作者：
Saif，M. Taher A.
中科院分区：
文献类型：
--
作者：
Joy，Md Saddam Hossain;Nall，Duncan L.;Saif，M. Taher A.
大脑中的神经元通过它们的突触相互交流。长期以来，人们一直认为这种交流是通过生物化学过程发生的。在这里，我们揭示了神经元中的机械张力对通信至关重要。使用体外大鼠海马神经元，我们发现1）神经元在形成突触后变得紧张/紧张，导致收缩性神经网络，以及2）没有这种收缩性，神经元无法放电。为了测量3D（而不是2D）细胞外基质中网络收缩性的时间演变，我们开发了一种具有1 nN分辨率的超灵敏力传感器。我们采用多电极阵列和iGluSnFR，谷氨酸传感器，分别在网络和单突触尺度上量化神经元放电。当神经元收缩性放松时，两种技术都显示出显著减少的放电。当收缩性恢复时，放电恢复。这一发现突出了神经收缩在基本脑功能中的重要贡献，并对我们理解神经生理学产生了影响。
Neurons in the brain communicate with each other at their synapses. It has long been understood that this communication occurs through biochemical processes. Here, we reveal that mechanical tension in neurons is essential for communication. Using in vitro rat hippocampal neurons, we find that 1) neurons become tout/tensed after forming synapses resulting in a contractile neural network, and 2) without this contractility, neurons fail to fire. To measure time evolution of network contractility in 3D (not 2D) extracellular matrix, we developed an ultrasensitive force sensor with 1 nN resolution. We employed Multi-Electrode Array and iGluSnFR, a glutamate sensor, to quantify neuronal firing at the network and at the single synapse scale, respectively. When neuron contractility is relaxed, both techniques show significantly reduced firing. Firing resumes when contractility is restored. This finding highlights the essential contribution of neural contractility in fundamental brain functions and has implications for our understanding of neural physiology.