Toward circuits optogenetics

Since the discovery of Channelrhodopsin and the first demonstration of photo-evoked action potentials in mammalian cells, optogenetics is progressively revolutionizing neuroscience research, opening perspectives both in fundamental and in medical research still unimaginable until few years ago.
Joint progress in light delivering approaches, multi-photon laser sources development, and opsins engineering has now brought the field of optogenetics into a new phase that we can name “circuit optogenetics”, where neural circuits distributed between different brain areas can be optically interrogated and controlled with millisecond temporal precision and single-cell resolution. Here, we review the main achievements in each of this field and anticipate the future needs that will make it possible to enlarge even more the use of optogenetics for brain circuits manipulation. We will also present a theoretical model and its experimental validation to predict light spreading and temperature rise induced under the typical illumination conditions used for two-photon optogenetics, including holographic and spiral scanning illumination.
Finally, we will present an example of circuits optogenetics, where we combined 2P multi-target temporally focused holographic illumination with a 2P scanning microscope to dissect how rod bipolar cells contribute to shape ganglion cell direction selectivity.