Novel X-ray Fluorescent Organic Monomer and Polymer Materials for Optogenetic Applications

French, David N.; Cannon, Kelli E.; Bartley, Aundrea F.; McMahon, Lori L.; Gray, Gary M.

doi:10.1364/translational.2018.jtu3a.55

Cited by 6 publications

(4 citation statements)

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“…Efforts are ongoing to develop and refine minimally invasive strategies for the generation of light within the brain to combat the challenges mentioned above (Chen et al, 2018). One potential strategy could employ the use of x-rays to activate radioluminescent materials (Berry et al, 2015; French et al, 2018; Shuba, 2019). Radioluminescence is the production of visible light by a material exposed to ionizing radiation.…”

Section: Introductionmentioning

confidence: 99%

LSO:Ce Inorganic Scintillators Are Biocompatible With Neuronal and Circuit Function

Bartley

Abiraman

Stewart

et al. 2019

Front. Synaptic Neurosci.

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Optogenetics is widely used in neuroscience to control neural circuits. However, non-invasive methods for light delivery in brain are needed to avoid physical damage caused by current methods. One potential strategy could employ x-ray activation of radioluminescent particles (RPLs), enabling localized light generation within the brain. RPLs composed of inorganic scintillators can emit light at various wavelengths depending upon composition. Cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light in response to x-ray or ultraviolet (UV) stimulation, could potentially be used to control neural circuits through activation of channelrhodopsin-2 (ChR2), a light-gated cation channel. Whether inorganic scintillators themselves negatively impact neuronal processes and synaptic function is unknown, and was investigated here using cellular, molecular, and electrophysiological approaches. As proof of principle, we applied UV stimulation to 4 μm LSO:Ce particles during whole-cell recording of CA1 pyramidal cells in acute hippocampal slices from mice that expressed ChR2 in glutamatergic neurons. We observed an increase in frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs), indicating activation of ChR2 and excitation of neurons. Importantly, LSO:Ce particles did not affect survival of primary mouse cortical neurons, even after 24 h of exposure. In extracellular dendritic field potential recordings, no change in the strength of basal glutamatergic transmission was observed during exposure to LSO:Ce microparticles. However, the amplitude of the fiber volley was slightly reduced with high stimulation. Additionally, there was a slight decrease in the frequency of sEPSCs in whole-cell voltage-clamp recordings from CA1 pyramidal cells, with no change in current amplitudes. The amplitude and frequency of spontaneous inhibitory postsynaptic currents were unchanged. Finally, long term potentiation (LTP), a synaptic modification believed to underlie learning and memory and a robust measure of synaptic integrity, was successfully induced, although the magnitude was slightly reduced. Together, these results show LSO:Ce particles are biocompatible even though there are modest effects on baseline synaptic function and long-term synaptic plasticity. Importantly, we show that light emitted from LSO:Ce particles is able to activate ChR2 and modify synaptic function. Therefore, LSO:Ce inorganic scintillators are potentially viable for use as a new light delivery system for optogenetics.

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Section: Introductionmentioning

confidence: 99%

LSO:Ce Inorganic Scintillators Are Biocompatible With Neuronal and Circuit Function

Bartley

Abiraman

Stewart

et al. 2019

Front. Synaptic Neurosci.

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show abstract

“…One potential strategy for less invasive light delivery to the brain is the use of X-rays to activate radioluminescent materials (Shuba, 2014;French et al, 2018;Bartley et al, 2019;. Radioluminescence is produced by exposing scintillating material to ionizing radiation, thereby causing generation of visible light.…”

Section: Introductionmentioning

confidence: 99%

“…One potential strategy for less invasive light delivery to the brain is the use of x-rays to activate radioluminescent materials [18][19][20][21] located within the brain. Radioluminescence is produced when a scintillating material absorbs ionizing radiation and re-emits a portion of the absorbed energy as visible light.…”

Section: Introductionmentioning

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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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.

show abstract

Section: Introductionmentioning

confidence: 99%

X-ray mediated scintillation increases synaptic activity via Cerium-doped LSO and Channelrhodopsin-2

Bartley

Fischer

Bagley

et al. 2020

Preprint

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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 light-sensitive 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, X-ray 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.

show abstract

Novel X-ray Fluorescent Organic Monomer and Polymer Materials for Optogenetic Applications

Cited by 6 publications

References 0 publications

LSO:Ce Inorganic Scintillators Are Biocompatible With Neuronal and Circuit Function

LSO:Ce Inorganic Scintillators Are Biocompatible With Neuronal and Circuit Function

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

X-ray mediated scintillation increases synaptic activity via Cerium-doped LSO and Channelrhodopsin-2

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