High-Density Optophysiology Platform for Recording Intracellular and Extracellular Signals across the Brain of Free-Moving Animals

Developing a novel tool capable of real-time monitoring and simultaneously quantifying of both intra/extracellular chemical signals across the large-scale brain is the key bottleneck for understanding the interactions between the molecules inside and outside neurons. Here we built up a high-density intra/extracellular optophysiology platform, together with developing two probes for specific recognition of L-cysteine (Cys) and dopamine (DA), for simultaneously quantifying of both intracellular Cys and extracellular DA with high selectivity and accuracy across the brain of freely moving animals, as well as recording electrical signals. Using this powerful tool, it was found that intracellular Cys regulated extracellular DA through inducing the expression of tyrosine hydroxylase in the depressed mice brain. We also established the functional networks of Cys and DA across 32 brain regions in freely moving animals. More importantly, it was discovered that depression reduced the correlations between adjacent brain regions, which was recovered by the treatment of N-acetyl-l-cysteine.