NeuroResource Monolithically Integrated m LEDs on Silicon Neural Probes for High-Resolution Optogenetic Studies in Behaving Animals

Highlights d Multiple mLEDs and recording sites were fabricated monolithically on silicon d Spikes were robustly induced using ultra-low optical power (60 nW) d Neurons 50 mm apart were controlled independently in CA1 of freely moving mice d Deep and superficial parts of CA pyramidal layer form distinct ripple generators In Brief Recording and stimulating multiple individual neurons is critical for local circuit analysis. Wu et al. fabricated neuron-size mLEDs directly on silicon shanks integrated with recording sites, controlling distinct cells and field oscillations in freely moving mice with unprecedented spatial resolution. SUMMARY We report a scalable method to monolithically integrate microscopic light emitting diodes (mLEDs) and recording sites onto silicon neural probes for op-togenetic applications in neuroscience. Each mLED and recording site has dimensions similar to a pyra-midal neuron soma, providing confined emission and electrophysiological recording of action potentials and local field activity. We fabricated and implanted the four-shank probes, each integrated with 12 mLEDs and 32 recording sites, into the CA1 pyramidal layer of anesthetized and freely moving mice. Spikes were robustly induced by 60 nW light power, and fast population oscillations were induced at the microwatt range. To demonstrate the spatiotemporal precision of parallel stimulation and recording, we achieved independent control of distinct cells $50 mm apart and of differential somato-dendritic compartments of single neurons. The scalability and spatiotemporal resolution of this monolithic optogenetic tool provides versatility and precision for cellular-level circuit analysis in deep structures of intact, freely moving animals.