scholarly journals Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Suhan Senova ◽  
Ilona Scisniak ◽  
Chih-Chieh Chiang ◽  
Isabelle Doignon ◽  
Stéphane Palfi ◽  
...  

Abstract Optogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic effects and did not trigger non-physiological functional activation. This study demonstrates the ability to illuminate cortical layers to a depth of several millimeters using pulsed red light without detrimental thermal damages.

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Suhan Senova ◽  
Ilona Scisniak ◽  
Chih-Chieh Chiang ◽  
Isabelle Doignon ◽  
Stéphane Palfi ◽  
...  

2018 ◽  
Vol 120 (1) ◽  
pp. 149-161 ◽  
Author(s):  
Sarah Libbrecht ◽  
Luis Hoffman ◽  
Marleen Welkenhuysen ◽  
Chris Van den Haute ◽  
Veerle Baekelandt ◽  
...  

Optogenetic manipulations are widely used for investigating the contribution of genetically identified cell types to behavior. Simultaneous electrophysiological recordings are less common, although they are critical for characterizing the specific impact of optogenetic manipulations on neural circuits in vivo. This is at least in part because combining photostimulation with large-scale electrophysiological recordings remains technically challenging, which also poses a limitation for performing extracellular identification experiments. Currently available interfaces that guide light of the appropriate wavelength into the brain combined with an electrophysiological modality suffer from various drawbacks such as a bulky size, low spatial resolution, heat dissipation, or photovoltaic artifacts. To address these challenges, we have designed and fabricated an integrated ultrathin neural interface with 12 optical outputs and 24 electrodes. We used the device to measure the effect of localized stimulation in the anterior olfactory cortex, a paleocortical structure involved in olfactory processing. Our experiments in adult mice demonstrate that because of its small dimensions, our novel tool causes far less tissue damage than commercially available devices. Moreover, optical stimulation and recording can be performed simultaneously, with no measurable electrical artifact during optical stimulation. Importantly, optical stimulation can be confined to small volumes with approximately single-cortical layer thickness. Finally, we find that even highly localized optical stimulation causes inhibition at more distant sites. NEW & NOTEWORTHY In this study, we establish a novel tool for simultaneous extracellular recording and optogenetic photostimulation. Because the device is built using established microchip technology, it can be fabricated with high reproducibility and reliability. We further show that even very localized stimulation affects neural firing far beyond the stimulation site. This demonstrates the difficulty in predicting circuit-level effects of optogenetic manipulations and highlights the importance of closely monitoring neural activity in optogenetic experiments.


1979 ◽  
Vol 310 (1) ◽  
pp. 25-33 ◽  
Author(s):  
D. L. Nelson ◽  
A. Herbet ◽  
L. Pichat ◽  
J. Glowinski ◽  
M. Hamon
Keyword(s):  

2014 ◽  
Vol 90 ◽  
pp. 157-165
Author(s):  
Suchinder K. Sharma ◽  
D. Gourier ◽  
B. Viana ◽  
T. Maldiney ◽  
E. Teston ◽  
...  

ZnGa2O4(ZGO) is a normal spinel. When doped with Cr3+ions, ZGO:Cr becomes a high brightness persistent luminescence material with an emission spectrum perfectly matching the transparency window of living tissues. It allowsin vivomouse imaging with a better signal to background ratio than classical quantum dots. The most interesting characteristic of ZGO:Cr lies in the fact that its LLP can be excited with red light, well below its band gap energy and in the transparency window of living tissues. A mechanism based on the trapping of carriers localized around a special type of Cr3+ions namely CrN2can explain this singularity. The antisite defects of the structure are the main responsible traps in the persistent luminescence mechanism. When located around Cr3+ions, they allow, via Cr3+absorption, the storage of not only UV light but also all visible light from the excitation source.


Cephalalgia ◽  
2017 ◽  
Vol 38 (7) ◽  
pp. 1215-1224 ◽  
Author(s):  
Yonglie Zhao ◽  
Margarida Martins-Oliveira ◽  
Simon Akerman ◽  
Peter J Goadsby

Background Migraine is a highly prevalent and disabling disorder of the brain with limited therapeutic options, particularly for preventive treatment. There is a need to identify novel targets and test their potential efficacy in relevant preclinical migraine models. Traditional Chinese medicines have been used for millennia and may offer avenues for exploration. Methods We evaluated two traditional Chinese medicines, gastrodin and ligustrazine, and compared them to two Western approaches with propranolol and levetiracetam, one effective and one ineffective, in an established in vivo rodent model of nociceptive durovascular trigeminal activation. Results Intravenous gastrodin (30 and 100 mg/kg) significantly inhibited nociceptive dural-evoked neuronal firing in the trigeminocervical complex. Ligustrazine (10 mg/kg) and propranolol (3 mg/kg) also significantly inhibited dural-evoked trigeminocervical complex responses, although the timing of responses of ligustrazine does not match its pharmacokinetic profile. Levetiracetam had no effects on trigeminovascular responses. Conclusion Our data suggest gastrodin has potential as an anti-migraine treatment, whereas ligustrazine seems less promising. Interestingly, in line with clinical trial data, propranolol was effective and levetiracetam not. Exploration of the mechanisms and modelling effects of Chinese traditional therapies offers novel route for drug discovery in migraine.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Jan C. Frankowski ◽  
Andrzej T. Foik ◽  
Alexa Tierno ◽  
Jiana R. Machhor ◽  
David C. Lyon ◽  
...  

AbstractPrimary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effects of traumatic brain injury on visual circuit function. Here we used anatomy and in vivo electrophysiological recordings in adult mice to quantify neuron responses to visual stimuli two weeks and three months after mild controlled cortical impact injury to primary visual cortex (V1). We found that, although V1 remained largely intact in brain-injured mice, there was ~35% reduction in the number of neurons that affected inhibitory cells more broadly than excitatory neurons. V1 neurons showed dramatically reduced activity, impaired responses to visual stimuli and weaker size selectivity and orientation tuning in vivo. Our results show a single, mild contusion injury produces profound and long-lasting impairments in the way V1 neurons encode visual input. These findings provide initial insight into cortical circuit dysfunction following central visual system neurotrauma.


2021 ◽  
Author(s):  
Agnès Trébuchon ◽  
F.-Xavier Alario ◽  
Catherine Liégeois-Chauvel

The posterior part of the superior temporal gyrus (STG) has long been known to be a crucial hub for auditory and language processing, at the crossroad of the functionally defined ventral and dorsal pathways. Anatomical studies have shown that this “auditory cortex” is composed of several cytoarchitectonic areas whose limits do not consistently match macro-anatomic landmarks like gyral and sulcal borders. The functional characterization of these areas derived from brain imaging studies has some limitations, even when high field functional magnetic resonance imaging (fMRI) is used, because of the variability observed in the extension of these areas between hemispheres and individuals. In patients implanted with depth electrodes, in vivo recordings and direct electrical stimulations of the different sub-parts of the posterior STG allow to delineate different auditory sub-fields in Heschl’s gyrus (HG), Planum Temporale (PT), the posterior part of the superior temporal gyrus anterior to HG, the posterior superior temporal sulcus (STS), and the region at the parietal-temporal boundary commonly labelled “Spt”. We describe how this delineation can be achieved using data from electrical cortical stimulation combined with local field potentials and time frequency analysis recorded as responses to pure tones and syllables. We show the differences in functional roles between the primary and non-primary auditory areas, in the left and the right hemispheres. We discuss how these findings help understanding the auditory semiology of certain epileptic seizures and, more generally, the neural substrate of hemispheric specialization for language.


PLoS Biology ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. e3001154
Author(s):  
Min-Hee Yi ◽  
Yong U. Liu ◽  
Anthony D. Umpierre ◽  
Tingjun Chen ◽  
Yanlu Ying ◽  
...  

Spinal microglia are highly responsive to peripheral nerve injury and are known to be a key player in pain. However, there has not been any direct evidence showing that selective microglial activation in vivo is sufficient to induce chronic pain. Here, we used optogenetic approaches in microglia to address this question employing CX3CR1creER/+: R26LSL-ReaChR/+ transgenic mice, in which red-activated channelrhodopsin (ReaChR) is inducibly and specifically expressed in microglia. We found that activation of ReaChR by red light in spinal microglia evoked reliable inward currents and membrane depolarization. In vivo optogenetic activation of microglial ReaChR in the spinal cord triggered chronic pain hypersensitivity in both male and female mice. In addition, activation of microglial ReaChR up-regulated neuronal c-Fos expression and enhanced C-fiber responses. Mechanistically, ReaChR activation led to a reactive microglial phenotype with increased interleukin (IL)-1β production, which is likely mediated by inflammasome activation and calcium elevation. IL-1 receptor antagonist (IL-1ra) was able to reverse the pain hypersensitivity and neuronal hyperactivity induced by microglial ReaChR activation. Therefore, our work demonstrates that optogenetic activation of spinal microglia is sufficient to trigger chronic pain phenotypes by increasing neuronal activity via IL-1 signaling.


1991 ◽  
Vol 46 (11-12) ◽  
pp. 1038-1044 ◽  
Author(s):  
Michel Havaux ◽  
Murielle Eyletters

Abstract Preillumination of intact pea leaves with a strong blue-green light of 400 W m-2 markedly inhibited both photoacoustically monitored O2-evolution activity and PS II photochemistry as estimated from chlorophyll fluorescence measurements. The aim of the present work was to examine, with the help of the photoacoustic technique, whether this high-light treatment deteriorated the in vivo PS I function too. High-frequency photoacoustic measurements indicated that photochemical conversion of far-red light energy in PS I was preserved (and even transiently stimulated) whereas photochemical energy storage monitored in light exciting both PS I and PS II was markedly diminished. Low-frequency photoacoustic measurements of the Emerson enhancement showed a spectacular change in the PS II/PS I activity balance in favor of PS I. It was also observed that the linear portion of the saturation curve of the far-red light effect in the Emerson enhancement was not changed by the light treatment. Those results lead to the conclusion that, in contrast to PS II, the in vivo PS I photofunctioning was resistant to strong light stress, thus confirming previous suggestions derived from in vitro studies. Estimation of the redox state of the PS I reaction center by leaf absorbance measurements at ca. 820 nm suggested that, under steady illumination, a considerably larger fraction of PS I centers were in the closed state in high-light pretreated leaves as compared to control leaves, presumably allowing passive adjustment of the macroscopic quantum yield of PS I photochemis­ try to the strongly reduced photochemical efficiency of photoinhibited PS II.


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