LITE-1 Dependent X-Ray Sensitivity in <i>C. elegans</i>

Cannon, Kelli E.; Ranasinghe, Meenakshi; Do, A.N.; Pierce, Hannah; Millhouse, Paul W.; Roychowdhury, Ayona; Foulger, Stephen H.; Dobrunz, Lynn E.; Anker, Jeffrey N.; Bolding, Mark

doi:10.1101/766568

Cited by 2 publications

(2 citation statements)

References 21 publications

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“…Multiple proteins can be altered and/or directly activated by x-rays, including rhodopsin [41,[57][58][59][60]. Recently, LITE-1, a UV light sensitive GPCR in C. elegans, has been discovered to also be activated by x-rays, producing behavioral effects [43]. However, to our knowledge, none of the opsins typically used for optogenetics have ever been tested for x-ray sensitivity.…”

Section: Discussionmentioning

confidence: 99%

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Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics

Bartley¹,

Fischer²,

Bagley³

et al. 2021

J. Neural Eng.

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Optogenetics is a widely used tool for studying neural circuits. However, non-invasive methods for light delivery in the brain are needed to avoid physical damage typically caused by intracranial insertion of light guides. An innovative strategy could employ X-ray activation of radioluminescent particles (RLPs) to emit localized light. We previously reported that RLPs composed of cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light, are biocompatible with neuronal function and synaptic transmission. However, little is known about the consequences of acute X-ray exposure on synaptic function and long-term plasticity. Furthermore, modulation of neuronal or synaptic function by X-ray induced radioluminescence from RLPs has not yet been demonstrated. Here we show that 30 minutes of X-ray exposure at a rate of 0.042 Gy/second caused no change in the strength of basal glutamatergic transmission during extracellular dendritic field recordings in mouse hippocampal slices. Additionally, long-term potentiation (LTP), a robust measure of synaptic integrity, was able to be induced after X-ray exposure and expressed at a magnitude not different from control conditions (absence of X-rays). This is important as synaptic plasticity is critical to learning and memory. Next, we used molecular and electrophysiological approaches to determine if X-ray dependent radioluminescence emitted from RLPs can activate light sensitive proteins. We found that X-ray stimulation of RLPs elevated cAMP levels in HEK293T cells expressing OptoXR, a chimeric opsin receptor that combines the extracellular lightsensitive domain of channelrhodopsin-2 (ChR2) with an intracellular second messenger signaling cascade. This demonstrates that X-ray radioluminescence from LSO:Ce particles can activate OptoXR. Next, we tested whether X-ray activation of the RLPs can enhance synaptic activity in whole-cell recordings from hippocampal neurons expressing ChR2, both in cell culture and acute hippocampal slices. Importantly, Xray radioluminescence caused an increase in the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in both systems, indicating activation of ChR2 and excitation of neurons. Together, our results show that X-ray activation of LSO:Ce particles can heighten cellular and synaptic function. The combination of LSO:Ce inorganic scintillators and X-rays is therefore a viable method for optogenetics as an alternative to more invasive light delivery methods.

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Section: Discussionmentioning

confidence: 99%

“…Several photosensitive proteins can be activated by xrays exposure [41,42], especially ones that respond to UV light [43]. Channelrhodopsin-2 (ChR2), a lightgated cation channel, can be activated by wavelengths in the UV range [21], as well as visible light [44].…”

Section: X-ray Exposure Does Not Directly Activate Chr2mentioning

confidence: 99%

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics

Bartley¹,

Fischer²,

Bagley³

et al. 2021

J. Neural Eng.

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X-ray perception: Animal studies of sensory and behavioral responses to X-rays

Mantraratnam

Bonnet

Rowe

et al. 2022

Front. Cell. Neurosci.

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Since their discovery in 1895, many studies have been conducted to understand the effect of X-rays on neural function and behavior in animals. These studies examined a range of acute and chronic effects, and a subset of studies has attempted to determine if X-rays can produce any sensory responses. Here we review literature on animal behavioral responses to X-rays from 1895 until 2021 to assess the evidence for detection of X-rays by sensory receptors in animals. We focus on the changes in appetitive and consummatory behavior, radiotaxis, behavioral arousal, and olfactory responses to X-rays that have been reported in the literature. Taken together, the reviewed literature provides a large body of evidence that X-rays can induce sensory responses in a wide variety of animals and also suggests that these responses are mediated by known sensory receptors. Furthermore, we postulate the role of reactive oxygen species (ROS), the most biologically active byproduct of X-rays, as a key mediator of sensory receptor responses to X-rays.

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LITE-1 Dependent X-Ray Sensitivity in C. elegans

Cited by 2 publications

References 21 publications

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics

Feasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics

X-ray perception: Animal studies of sensory and behavioral responses to X-rays

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