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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. 

Abstract 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 a previously unrecognized paradigm wherein mechanical tension in neurons is essential for communication. Usingin vitrorat 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 (not2D) extracellular matrix, we developed an ultra-sensitive force sensor with 1 nN resolution. We employed Multi-Electrode Array (MEA) 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. Neural contractility may play a crucial role in memory, learning, cognition, and various neuropathologies. 

Abstract Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro‐electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built‐in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell‐derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long‐term recording. Overall, this technology, termed “mind in vitro” to underscore the computing inspiration, provides an end‐to‐end solution that can be widely deployed due to its affordable (>10× cost reduction) and open‐source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.