An all-optical system for rapid and deep interrogation of behaviorally relevant activity patterns (Conference Presentation)

Holographic optogenetics is an emerging tool for distributed control of spatiotemporal neuronal activity. Establishing causality between specific sequences of neuronal activity and behavior requires manipulating this code at the level of individual neurons while recording neural responses and behavioral readout. However, traditional methods of optogenetic perturbation lack the ability to emulate natural patterns of neural activity, or to rapidly alter the activity of specific neurons deep in the brain. To address the goal of producing behaviorally relevant sequences of neural activity, we have developed an all-optical, rapid two-photon optogenetic stimulation and imaging system with cellular resolution and 5 ms temporal precision. Using an amplified laser with high peak pulse power, together with wavefront shaping methods using a fast spatial light modulator (3 ms switching time), we were able to stimulate dozens of neurons deep in the olfactory bulb (>350 µm) at a high rate (>100 Hz) with cellular resolution. We optimized the system parameters to enable efficient excitation with a low power budget, to enable the simultaneous stimulation of many cells (~60). We then demonstrated stimulation of mitral and tufted cells, the projection neurons of the olfactory bulb, at a high rate, generating artificial odor-evoked responses. We will present the system characteristics and discuss its potential applications for manipulating and reading neuronal activity on a behaviorally relevant spatiotemporal scale to dissect the activity codes that guide behavior across different modalities.