Towards translational optogenetics

Bansal, Akshaya; Shikha, Swati; Zhang, Yong

doi:10.1038/s41551-021-00829-3

Cited by 86 publications

(95 citation statements)

References 219 publications

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“…Such tethered optical fibers largely restrict the freedom of movement that leads to motion artifacts; moreover, cumbersome and time‐consuming fixation processes, connections, and stable attachment also limit its applications. [ 36 ] Recently, great efforts have been made to develop wireless optogenetic technology based on light emitting diodes (LEDs). [ 35,37 ] Even though implantable LED devices and associated powering circuits have become smaller, lighter, and more versatile to enable dual‐color/dual‐channel optogenetics, the requirement for electronic components still complicates the fabrication and implementation procedures.…”

Section: Discussionmentioning

confidence: 99%

3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals

Lin

Sun

Tang

et al. 2022

Adv Healthcare Materials

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Upconversion techniques offer all-optical wireless alternatives to modulate targeted neurons in behaving animals, but most existing upconversion-based optogenetic devices show prefixed emission that is used to excite just one channelrhodopsin at a restricted brain region. Here, a hierarchical upconversion device is reported to enable spatially selective and combinatory optogenetics in behaving rodent animals. The device assumes a multiarrayed optrode format containing engineered upconversion nanoparticles (UCNPs) to deliver dynamic light palettes as a function of excitation wavelength. Three primary emissions at 477, 540, and 654 nm are selected to match the absorption of different channelrhodopsins. The UCNPs are barcode assembled to multiple nanomachined optical pinholes in a microscale pipette device to allow remotely addressable, spectrum programmable, and spatially selective optical interrogation of complex brain circuits. Using the unique device, the basolateral amygdala and caudoputamen circuits are selectively modulated and the associated fear or anxiety behavior in freely behaving rodents is successfully differentiated. It is believed that the 3D barcode upconversion device would be a great supplement to current optogenetic toolsets and opens up new possibilities for sophisticated neural control.

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Section: Discussionmentioning

confidence: 99%

3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals

Lin

Sun

Tang

et al. 2022

Adv Healthcare Materials

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“…With the discovery of optogenetics [4,5] and infrared neuromodulation (INM) [6,7], light-induced control of neurons with high spatiotemporal resolution became one of the most powerful tools in neuroscience [8]. Therefore, new milestones have been set within the biotechnology community for novel devices able to deliver light in localized brain regions across the full electromagnetic spectrum [9][10][11]. Interrogation of the brain signals is a complex task and thus it requires bi-directional interfaces integrated with multiple functionalities in a single monolithic structure.…”

Section: Introductionmentioning

confidence: 99%

Opsin-free optical neuromodulation and electrophysiology enabled by a soft monolithic infrared multifunctional neural interface

Meneghetti

Kaur

Sui

et al. 2022

Preprint

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Controlling neuronal activity with high spatial resolution using multifunctional and minimally invasive neural interfaces constitutes an important step towards developments in neuroscience and novel treatments for brain diseases. While infrared neuromodulation is an emerging technology for controlling the neuronal circuitry, it lacks soft implantable monolithic interfaces capable of simultaneously delivering light and recording electrical signals from the brain while being mechanically brain-compatible. Here, we have developed a soft fibre-based device based on high-performance thermoplastics which are >100-fold softer than silica glass. The presented fibre-implant is capable of safely neuromodulating the brain activity in localized cortical domains by delivering infrared laser pulses in the 2 μm spectral region while recording electrophysiological signals. Action and local field potentials were recorded in vivo in adult rats while immunohistochemical analysis of the tissue indicated limited microglia and monocytes response introduced by the fibre and the infrared pulses. We expect our devices to further enhance infrared neuromodulation as a versatile approach for fundamental research and clinically translatable therapeutic interventions.

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“…Over the last several years, there has been great interest in controlling the activity of proteins with light (1–8). The field of ‘optogenetics’ has expanded our understanding, in situ , of the role of specific proteins in signal transduction, and especially, how neuronal processes are controlled (9–11).…”

Section: Introductionmentioning

confidence: 99%

Allosteric inactivation of an engineered optogenetic GTPase

Jain¹,

Dokholyan

Lee

2022

Preprint

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Optogenetics is a technique for establishing direct spatiotemporal control over molecular function within living cells using light. Light application induces conformational changes within targeted proteins that produce changes in function. One of the applications of optogenetic tools is an allosteric control of proteins via light-sensitive LOV2 domain, which allows direct and robust control of protein function. Computational studies supported by cellular imaging demonstrated that application of light allosterically controlled signaling proteins Vav2, ITSN, and Rac1, but the structural and dynamic basis of such control has yet to be elucidated by experiment. Here, using NMR spectroscopy, we discover principles of action of allosteric control of cell division control protein 42 (CDC42), a small GTPase involved in cell signaling. Both LOV2 and Cdc42 employ flexibility in their function to switch between “dark”/ “lit” or active/inactive states, respectively. By conjoining Cdc42 and LOV2 domains into the bi-switchable fusion Cdc42Lov, application of light – or alternatively, mutation in LOV2 to mimic light absorption – allosterically inhibits Cdc42 downstream signaling. The flow and patterning of allosteric transduction in this flexible system is well-suited to observation by NMR. Close monitoring of the structural and dynamic properties of dark versus lit states of Cdc42Lov revealed lit-induced allosteric perturbations. Chemical shift perturbations for lit mimic, I539E, have distinct regions of sensitivity and both the domains are coupled together leading to bi-directional interdomain signaling. Insights gained from this optoallosteric design will increase our ability to control response sensitivity in future designs.Significance StatementControl of cell signaling activity in proteins by light is one of the primary goals of optogenetics. The hybrid light-receptor/cell-signaling protein Cdc42Lov was engineered recently as an optogenetic tool, employing a novel allosteric strategy that results in photoinhibition. In contrast to previous activation designs, the mechanism of inhibition of GTPase signaling activity in Cdc42 is only apparent at a detailed structural and dynamic level. NMR characterization of dark and mutationally “lit” forms reveals the allosteric interdomain perturbations, knowledge of which will enhance future applications of this design strategy.

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Towards translational optogenetics

Cited by 86 publications

References 219 publications

3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals

3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals

Opsin-free optical neuromodulation and electrophysiology enabled by a soft monolithic infrared multifunctional neural interface

Allosteric inactivation of an engineered optogenetic GTPase

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