Mapping Large-scale Spatiotemporal Dynamics of Synaptic Plasticity and LTP for Memory Encoding in the Hippocampal Network

Understanding memory formation requires elucidating the intricate dynamics of neuronal networks in the hippocampus, where information is encoded and processed through specific activity patterns and synaptic plasticity. Here, we introduce “EVOX,” an advanced network electrophysiology platform equipped with high-density microelectrode arrays to capture critical network-level synaptic dynamics integral to learning and memory. This platform surpasses traditional methods by enabling label-free, high-order mapping of neural interactions, providing unprecedented insights into network Long-Term Potentiation (LTP) and evoked synaptic transmission within the hippocampal network. Utilizing EVOX, we demonstrate that high-frequency stimulation induces network-wide LTP, revealing enhanced synaptic efficacy in previously inactive cell assemblies in hippocampal layers. Our platform enables the real-time observation of network synaptic transmission, capturing the intricate patterns of connectivity and plasticity that underpin memory encoding. Advanced computational techniques further elucidate the mesoscale transmembrane generators and the dynamic processes that govern network-level memory encoding mechanisms. These findings uncover the complex dynamics that underlie learning and memory, showcasing EVOX’s potential to explore synaptic and cellular phenomena in aging circuits. EVOX not only advances our understanding of hippocampal memory mechanisms but also serves as a powerful tool to investigate the broader scope of neural plasticity and network interactions in healthy and diseased states.