All-optical interrogation of neural circuits

Abstract

There have been two recent revolutionary advances in neuroscience: First, genetically encoded activity sensors have brought the goal of optical detection of single action potentials in vivo within reach. Second, optogenetic actuators now allow the activity of neurons to be controlled with millisecond precision. These revolutions have now been combined, together with advanced microscopies, to allow “all-optical” readout and manipulation of activity in neural circuits with single-spike and single-neuron precision. This is a transformational advance that will open new frontiers inneuroscience research. Harnessing the power of light in the all-optical approach require scoexpression of genetic allyen code dactivity sensors and optogenetic probesin thes a meneurons, as well as the ability to simultaneously target and record the light from the selected neurons. It has recently become possible to combine sensors and optical strategies that are sufficiently sensitiveandcross talk free to enable single-actionpotential sensitivity and precision for both readout and manipulation in the intact brain. The combination of simultaneous readout and manipulation from the same geneticallyde fined cells will enable awiderange of new experiments as well as inspire new technologies forinter acting with the brain. The advances described in this review herald a future where the traditional tools used for generations by physiologists to study and interact with the brain—stimulation and recording electrodes—can largely be replaced by light. We outline potential future developments in this field and discuss how the all-optical strategy can be applied to solve fundamental problems in neuroscience.