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Tools for Analyzing and Controlling Brain Circuits
To enable the understanding and repair of complex biological systems such as the brain, we are creating novel optical tools that enable molecular-resolution maps of large scale systems, as well as technologies for observing and controlling high-speed physiological dynamics in such systems.
Noninvasive Optogenetics by Directed Evolution of Channelrhodopsins and AAV Vectors for Systemic Delivery Across the Blood Brain Barrier
Advanced optical methods for all-optical brain circuits manipulation
Abstract BodyAll-optical manipulation of neuronal circuits requires the control of a single or multiple neuron independently in space and time with single-spike precision and single-cell resolution. This is the next challenge to be faced in optogenetics imposing to move from whole-region optogenetics, using wide field visible light illumination, to what we named circuit optogenetics.
Indeed, in past years, joint progresses in complementary fields including opsin engineering, optical microscopy and multiphoton laser source development have provided the neuroscience community with a sophisticated optogenetics toolbox that has opened the door to neuronal circuits manipulation. Precisely, a large number of variants in microbial opsins have been recently engineered, to speed-up their kinetics, improve their conductance, confine their expression and shift their absorption peak. In parallel, advanced wavefront shaping approaches combined with two-photon excitation have been developed to precisely guide light through tissues using either scanning or parallel light shaping combined with temporal focusing. Furthermore, the combination of holographic light multiplexing with ad hoc spatiotemporal shaping approaches have been demonstrated to have the capability to generate patterned illumination at multiple axially distinct planes, thus enabling optical control of multiple targets within a 3D volume. All in all, these progresses have brought optogenetics into a new phase, circuit optogenetics, where we can determine how multiple parts of a circuit work together in an integrated fashion.
Here, I will review these progresses and show few examples of circuits optogenetics performed in different experimental paradigms.
Towards the Optical Cochlear Implant: Optogenetic Stimulation of the Auditory Pathway
When hearing fails, cochlear implants (CIs) provide open speech perception to most of the currently half a million CI users. CIs bypass the defective sensory organ and stimulate the auditory nerve electrically. The major bottleneck of current CIs is the poor coding of spectral information, which results from wide current spread from each electrode contact. As light can be more conveniently confined, optical stimulation of the auditory nerve presents a promising perspective for a fundamental advance of CIs. Moreover, given the improved frequency resolution of optical excitation and its versatility for arbitrary stimulation patterns the approach also bears potential for auditory research. Developing optogenetic stimulation for auditory research and future CIs requires efforts toward design and characterization of appropriate optogenetic actuators, viral gene transfer to the neurons, as well as engineering of multichannel optical CIs. The presentation will summarize the current state of optogenetic stimulation of the auditory pathway and report on recent breakthroughs on achieving high temporal fidelity and frequency resolution and establishing multichannel optical CIs.