One-step optogenetics with multifunctional flexible polymer fibers

Park, Seongjun; Guo, Yuanyuan; Jia, Xiaoting; Choe, Han Kyoung; Grena, Benjamin; Kang, Jeewoo; Park, Jiyeon; Lu, Chi; Canales, Andrés; Chen, Ritchie; Yim, Yeong Shin; Choi, Gloria B.; Fink, Yoel; Anikeeva, Polina

doi:10.1038/nn.4510

Cited by 321 publications

(412 citation statements)

References 49 publications

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“…These values are comparable to those previously obtained in thermally drawn polymer fibers [1.2-2.7 dB/cm]. [27][28][29][30] This makes our device suitable for controlling photoswitchable ligands with light across the visible spectrum. 22 Due to the absorbance of PC used as the waveguide core in the UV-A range, the optical loss at 365 nm was 2.03±0.15 dB/cm.…”

Section: Developing a Multifunctional Fiber For In Vivo Photopharmacosupporting

confidence: 87%

“…This onestep surgery reduces the tissue damage that may occur during multiple surgeries, and also ensures colocalization of the expression profile with the optical and pharmacological interrogation volume. 28 Six to eight weeks post-implantation, we confirmed TRPV1 expression and the fiber position in the VTA ( Fig. 3c, Supplementary Fig.…”

Section: In Vivo Photopharmacology Of Midbrain Dopaminergic Circuitssupporting

confidence: 64%

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In vivophotopharmacology enabled by multifunctional fibers

Frank

Antonini

Chiang

et al. 2020

Preprint

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To reversibly manipulate neural circuits with increased spatial and temporal control, photoswitchable ligands can add an optical switch to a target receptor or signaling cascade. This approach, termed photopharmacology, has been enabling to molecular neuroscience, however, its application to behavioral experiments has been impeded by a lack of integrated hardware capable of delivering both light and compounds to deep brain regions in moving subjects. Here, we devise a hybrid photochemical genetic approach to target neurons using a photoswitchable agonist of capsaicin receptor (TRPV1), red-AzCA-4. Using the thermal drawing process we created multifunctional fibers that can deliver viruses, photoswitchable ligands, and light to deep brain regions in awake, freely moving mice. We implanted our fibers into the ventral tegmental area (VTA), a midbrain hub of the mesolimbic pathway, and used them to deliver a transgene coding for TRPV1. This sensitized excitatory VTA neurons to red-AzCA-4, and allowed us to optically control conditioned place preference using a mammalian ion-channel, thus extending applications of photopharmacology to behavioral experiments. Applied to endogenous receptors, our approach may accelerate studies of molecular mechanisms underlying animal behavior. AUTHOR CONTRIBUTIONS JAF and PA conceived and coordinated the study. DBK synthesized the photoswitchable compounds. JAF and GR carried out imaging experiments in cultured neurons. JAF, MJA, and IG fabricated and characterized the multifunctional fibers. YF aided in fiber design. PC and FK produced lentiviral vectors. JAF, MJA, PC, AC, and IG performed immunohistochemical experiments. JAF and MJA performed the behavioral experiments. PC, AC, MJA, and JAF wrote scripts for data analysis. JAF, MJA, and PA wrote the manuscript with input from all co-authors.

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Section: Developing a Multifunctional Fiber For In Vivo Photopharmacosupporting

confidence: 87%

Section: In Vivo Photopharmacology Of Midbrain Dopaminergic Circuitssupporting

confidence: 64%

In vivophotopharmacology enabled by multifunctional fibers

Frank

Antonini

Chiang

et al. 2020

Preprint

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“…Optical fibers have been increasingly used in various biomedical fields such as optogenetics, phototherapy, laser surgery, optical sensing, and imaging . However, most of the optical fibers used are silica fibers or polycarbonate fibers with a high modulus, which tends to damage tissue . Organohydrogels are soft and have excellent transmittance.…”

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confidence: 99%

Mechanically and Electronically Robust Transparent Organohydrogel Fibers

et al. 2020

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Stretchable conductive fibers are key elements for next‐generation flexible electronics. Most existing conductive fibers are electron‐based, opaque, relatively rigid, and show a significant increase in resistance during stretching. Accordingly, soft, stretchable, and transparent ion‐conductive hydrogel fibers have attracted significant attention. However, hydrogel fibers are difficult to manufacture and easy to dry and freeze, which significantly hinders their wide range of applications. Herein, organohydrogel fibers are designed to address these challenges. First, a newly designed hybrid crosslinking strategy continuously wet‐spins hydrogel fibers, which are transformed into organohydrogel fibers by simple solvent replacement. The organohydrogel fibers show excellent antifreezing (< ‐80 °C) capability, stability (>5 months), transparency, and stretchability. The predominantly covalently crosslinked network ensures the fibers have a high dynamic mechanical stability with negligible hysteresis and creep, from which previous conductive fibers usually suffer. Accordingly, strain sensors made from the organohydrogel fibers accurately capture high‐frequency (4 Hz) and high‐speed (24 cm s−1) motion and exhibit little drift for 1000 stretch–release cycles, and are powerful for detecting rapid cyclic motions such as engine valves and are difficult to reach by previously reported conductive fibers. The organohydrogel fibers also demonstrate potential as wearable anisotropic sensors, data gloves, soft electrodes, and optical fibers.

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“…As implantable activity monitors, such as Graded-lndex (GRIN) lenses and multi-unit electrodes, continue to improve, we may soon be able to combine those technologies with this protocol 17,18 . By recording form relevant brain areas during olfactory learning, it is possible to probe how neuronal activities change during associative learning.…”

Section: Discussionmentioning

confidence: 99%

An Objective and Reproducible Test of Olfactory Learning and Discrimination in Mice

Liu

Patel

Tepe

et al. 2018

JoVE

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Olfaction is the predominant sensory modality in mice and influences many important behaviors, including foraging, predator detection, mating, and parenting. Importantly, mice can be trained to associate novel odors with specific behavioral responses to provide insight into olfactory circuit function. This protocol details the procedure for training mice on a Go/No-Go operant learning task. In this approach, mice are trained on hundreds of automated trials daily for 2–4 weeks and can then be tested on novel Go/No-Go odor pairs to assess olfactory discrimination, or be used for studies on how odor learning alters the structure or function of the olfactory circuit. Additionally, the mouse olfactory bulb (OB) features ongoing integration of adult-born neurons. Interestingly, olfactory learning increases both the survival and synaptic connections of these adult-born neurons. Therefore, this protocol can be combined with other biochemical, electrophysiological, and imaging techniques to study learning and activity-dependent factors that mediate neuronal survival and plasticity.

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One-step optogenetics with multifunctional flexible polymer fibers

Cited by 321 publications

References 49 publications

In vivophotopharmacology enabled by multifunctional fibers

In vivophotopharmacology enabled by multifunctional fibers

Mechanically and Electronically Robust Transparent Organohydrogel Fibers

An Objective and Reproducible Test of Olfactory Learning and Discrimination in Mice

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