This study investigates neural activity changes in the medial prefrontal cortex (mPFC) of a lipopolysaccharide (LPS)-induced acute depression mouse model using flexible polymer multichannel electrodes, local field potential (LFP) analysis, and a convolutional neural network-long short-term memory (CNN-LSTM) classification model. LPS treatment effectively induced depressive-like behaviors, including increased immobility in the tail suspension and forced swim tests, as well as reduced sucrose preference. These behavioral outcomes validate the LPS-induced depressive phenotype, providing a foundation for neurophysiological analysis. Flexible polymer-based electrodes enabled the long-term recording of high-quality LFP and spike signals from the mPFC. Time-frequency and power spectral density (PSD) analyses revealed a significant increase in theta band (3–8 Hz) amplitude under depressive conditions. Using theta waveform features extracted via empirical mode decomposition (EMD), we classified depressive states with a CNN-LSTM model, achieving high accuracy in both training and validation sets. This study presents a novel approach for depression state recognition using flexible polymer electrodes, EMD, and CNN-LSTM modeling, suggesting that heightened theta oscillations in the mPFC may serve as a neural marker for depression. Future studies may explore theta coupling across brain regions to further elucidate neural network disruptions associated with depression.
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