Opto‐chemogenetics with luminopsins: A novel avenue for targeted control of neuronal activity

Berglund, Ken; Gross, Robert E.

doi:10.1002/jnr.24473

Cited by 7 publications

(3 citation statements)

References 11 publications

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“…Taken with the roster of papers in the prior commentary (Berglund & Gross, ), these new BL‐OG papers further advance this technology, and underscore the utility and specificity of this approach (Table ).…”

Section: Nomenclatures Of Genetic Methods For Control Of Neural Activitymentioning

confidence: 71%

BL‐OG: BioLuminescent‐OptoGenetics

Moore

Berglund

2019

J of Neuroscience Research

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Section: Nomenclatures Of Genetic Methods For Control Of Neural Activitymentioning

confidence: 71%

BL‐OG: BioLuminescent‐OptoGenetics

Moore

Berglund

2019

J of Neuroscience Research

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“…This broad targeting can lead to side effects (Ostergard et al 2014;Cochran et al 2015). Optogenetics, conversely, combines light and genetic techniques to activate or inhibit speci c cells, offering temporal and spatial speci city (Berglund and Gross 2020). This eliminates the side effects associated with broader neuronal targeting and holds promise as a future pain therapy (Nagel et al 2002;Fortin et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Photogenetics Inhibits the Activity of Glutamate Neurons Projected from the Motor Cortex to the Ventroposterolateral Nucleus of the Thalamus to Alleviates Central Post-Stroke Pain in Rats

Deng,

Gu,

2024

Preprint

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The "central sensitization" and "central imbalance" theories suggest that central post-stroke pain (CPSP) is the result of neuronal overactivity and an imbalance between excitatory and inhibitory functions of the nervous system caused by damage to the sensory system. The ventral posterior lateral nucleus of the thalamus (VPL) and the primary motor cortex (M1) are key brain regions for nociceptive message transmission. However, the effects of inhibiting M1-VPL glutamatergic projections in CPSP remain unclear. his study investigates the efficacy of photogenetic inhibition of M1-VPL glutamatergic neuron excitability in a rat model of CPSP. CPSP rats underwent M1 injection with rAAV encoding an inhibitory photosensitive protein, followed by implantation of an optical fiber sleeve above the VPL and subsequent 10 W, 20 Hz, 5 ms yellow laser (589 nm) irradiation. The irradiation scheme was to start from the 3rd day after the CPSP mode, light for 2 min, turn off for 3 min, and repeat 6 times a day for 12 consecutive days. We observed that the mechanical and thermal pain thresholds were increased in CPSP rats, and the expressions of M1 pain-related factors c-Fos, vesicular glutamate transporter protein 2 (VGLUT2), and N-methyl-D-aspartate receptor subtype 2B (NR2B) were down-regulated. These findings indicate that photogenetic inhibition of M1-VPL glutamatergic projection can relieve pathologic pain in CPSP rats.

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“…Our NIR-triggered CMI has seamlessly integrated rapamycin@PDPP with chemogenetics, offering at least three aspects of advantages: 1. effective and robust control of FRB/FKBP binding (rapamycin); 2. high precision of spatiotemporal control at single-cell resolution (photosensitive nanoparticles); 3. deep tissue penetration with long-wavelength photostimulation (NIR) and high biocompatibility (nanomaterials and genetically-encoded modulators). With all these benefits including the unique feature of NIR 86,87 , we expect that our opto-chemogenetics prototype would be applicable broadly and particularly beneficial to future in vivo applications.…”

Section: Discussionmentioning

confidence: 99%

Opto-chemogenetic inhibition of L-type Ca_V1 channels in neurons through a membrane-assisted molecular linkage

Geng,

Yang,

et al. 2024

Preprint

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Acute, specific, and robust inhibition of L-type Ca2+ (CaV1) channels has been sought after for both research and therapeutic applications. Compared to other available CaV1 antagonists, genetically-encoded modulators, such as CMI (C-terminus mediated inhibition) peptides encoded by CaV1 DCT (distal C-terminus), hold great potentials due to its affirmative mechanisms of action on both gating and signaling. Here, we find that membrane-anchoring with a Ras tag could essentially help form a type of intramolecular-equivalent linkage, by which the tag anchored-peptide appears to dimerize with another protein or peptide on the membrane, supported by the evidence from patch-clamp electrophysiology and FRET imaging. We then design and implement the constitutive and inducible CMI modules, with appropriate dynamic ranges targeting the short and long variants of CaV1.3, both naturally occurring in neurons. Upon optical (infrared-responsive nanoparticles) and/or chemical (rapamycin) induction of FRB/FKBP binding, DCT peptides with no CMI in the cytosol acutely translocate onto the membrane via FRB-Ras, where the physical linkage requirement could be fulfilled. The peptides robustly produce acute and potent inhibitions on both recombinant CaV1.3 channels and neuronal CaV1 activities, and thus the Ca2+ influx-neuritogenesis coupling. Validated through opto-chemogenetic induction, this prototype demonstrates channel modulation via membrane-assisted molecular linkage, promising broad applicability to diverse membrane proteins.

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Opto‐chemogenetics with luminopsins: A novel avenue for targeted control of neuronal activity

Cited by 7 publications

References 11 publications

BL‐OG: BioLuminescent‐OptoGenetics

BL‐OG: BioLuminescent‐OptoGenetics

Photogenetics Inhibits the Activity of Glutamate Neurons Projected from the Motor Cortex to the Ventroposterolateral Nucleus of the Thalamus to Alleviates Central Post-Stroke Pain in Rats

Opto-chemogenetic inhibition of L-type Ca_V1 channels in neurons through a membrane-assisted molecular linkage

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Opto‐chemogenetics with luminopsins: A novel avenue for targeted control of neuronal activity

Cited by 7 publications

References 11 publications

BL‐OG: BioLuminescent‐OptoGenetics

BL‐OG: BioLuminescent‐OptoGenetics

Photogenetics Inhibits the Activity of Glutamate Neurons Projected from the Motor Cortex to the Ventroposterolateral Nucleus of the Thalamus to Alleviates Central Post-Stroke Pain in Rats

Opto-chemogenetic inhibition of L-type CaV1 channels in neurons through a membrane-assisted molecular linkage

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Product

Resources

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Opto-chemogenetic inhibition of L-type Ca_V1 channels in neurons through a membrane-assisted molecular linkage