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 frontiersinneuroscienceresearch.Harnessingthepoweroflightintheall-opticalapproachrequirescoexpressionofgeneticallyencodedactivity sensorsandoptogeneticprobesinthesameneurons,aswellastheabilitytosimultaneouslytargetandrecordthelightfromtheselectedneurons. It has recently become possible to combine sensors and optical strategies that are sufficiently sensitive and cross talk free to enable single-actionpotential sensitivity and precision for both readout and manipulation in the intact brain. The combination of simultaneous readout and manipulationfromthesamegeneticallydefinedcellswillenableawiderangeofnewexperimentsaswellasinspirenewtechnologiesforinteractingwith 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.

A better way to crack the brain

“…For example, a combination of advanced optical imaging and optogenetics can now read and write patterns of activity into populations of neurons 5 . It is also possible to relate firing patterns to the biology of the neurons being recorded, including their genetics and connectivity.…”

Intact skull chronic windows for mesoscopic wide-field imaging in awake mice

“…The current generation of optogenetic tools provides unprecedented possibilities for selectively mapping and manipulating network elements within the rodent brain (Emiliani et al, 2015). As a result, these methods are growing in popularity for studying the relationship between neuronal activity and behavior in awake mice.…”

Brain heating induced by near-infrared lasers during multiphoton microscopy

“…MODERN NEUROSCIENCE has been transformed by tools that use light to observe and manipulate brain cells (Chen et al 2013;Emiliani et al 2015;Hochbaum et al 2014). Optical methods allow spatially dense readout and optogenetic control of neurons in vivo with minimal perturbations of the brain.…”