Recording Network-based Synaptic Transmission and LTP in the Hippocampal Network on a Large-scale Biosensor

The process of learning and memory formation in the hippocampus is a complex phenomenon involving changes in synaptic efficiency that shape the connections between associated neurons. Long-term potentiation (LTP) is a widely used approach for studying activity-dependent synaptic plasticity in the hippocampus. However, conventional methods of measuring LTP using brain slices and low-density microelectrode arrays (MEAs) have limitations in spatial mapping and induction of inter-experiential variability. To overcome these challenges, we implemented a large-scale ex-vivo electrophysiological platform using a high-density CMOS-based biosensor. This approach allows simultaneous recordings of network-wide evoked synaptic responses and LTP in the hippocampal circuit. It provides a platform for large-scale spatial mapping of hippocampal synaptic activity-dependent changes modulated by external electrical stimulation and resultant network LTP in the corresponding SC pathway. This approach can potentially instantiate a large-scale model for learning and memory by identifying network LTP-induced signaling cascades and their mechanisms with applications for aging, disease, and pharmacology in the context of synaptic plasticity.