Open AccessFeasibility of cerium-doped LSO particles as a scintillator for x-ray induced optogenetics
Author(s) -
Aundrea F. Bartley,
Máté Fischer,
Micah E. Bagley,
Justin Barnes,
Mary K. Burdette,
Kelli E Can,
Mark Bolding,
Stephen H. Foulger,
Lori L. McMahon,
Jason P. Weick,
Lynn E. Dobrunz
Publication year - 2021
Publication title -
journal of neural engineering
Language(s) - English
Resource type - Journals
eISSN - 1741-2560
pISSN - 1741-2552
DOI - 10.1088/1741-2552/abef89
Subject(s) - radioluminescence , optogenetics , photostimulation , biophysics , neurotransmission , hippocampal formation , extracellular , long term potentiation , channelrhodopsin , chemistry , neuroscience , materials science , biology , scintillator , optics , receptor , physics , biochemistry , detector
Objective. Non-invasive light delivery into the brain is needed for in vivo optogenetics to avoid physical damage. An innovative strategy could employ x-ray activation of radioluminescent particles (RLPs) to emit localized light. However, modulation of neuronal or synaptic function by x-ray induced radioluminescence from RLPs has not yet been demonstrated. Approach. Molecular and electrophysiological approaches were used to determine if x-ray dependent radioluminescence emitted from RLPs can activate light sensitive proteins. RLPs composed of cerium doped lutetium oxyorthosilicate (LSO:Ce), an inorganic scintillator that emits blue light, were used as they are biocompatible with neuronal function and synaptic transmission. Main results. We show that 30 min of x-ray exposure at a rate of 0.042 Gy s -1 caused no change in the strength of basal glutamatergic transmission during extracellular field recordings in mouse hippocampal slices. Additionally, long-term potentiation, a robust measure of synaptic integrity, was induced after x-ray exposure and expressed at a magnitude not different from control conditions (absence of x-rays). 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 rhodopsin 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 channelrhodopsin-2, both in cell culture and acute hippocampal slices. Importantly, x-ray radioluminescence caused an increase in the frequency of spontaneous excitatory postsynaptic currents in both systems, indicating activation of channelrhodopsin-2 and excitation of neurons. Significance. 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.