Quantitative analysis of the optogenetic excitability of CA1 neurons

Frontiers in Computational Neuroscience

Neuroscience

Robrecht Raedt¹  Wout Joseph²  Thomas Tarnaud²  Emmeric Tanghe²  Laila Weyn³  Ruben Schoeters³ 

[1]4BRAIN, Department of Neurology, Institute for Neuroscience, Ghent University, Ghent, Belgium

[2]WAVES, Department of Information Technology (INTEC), Ghent University/IMEC, Ghent, Belgium

[3]WAVES, Department of Information Technology (INTEC), Ghent University/IMEC, Ghent, Belgium

[4]4BRAIN, Department of Neurology, Institute for Neuroscience, Ghent University, Ghent, Belgium

关键词: optogenetics;    cornu ammonis;    computational modeling;    NEURON;    tissue activation;    sensitivity analysis;   

DOI  :  10.3389/fncom.2023.1229715

 received in 2023-05-26, accepted in 2023-07-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionOptogenetics has emerged as a promising technique for modulating neuronal activity and holds potential for the treatment of neurological disorders such as temporal lobe epilepsy (TLE). However, clinical translation still faces many challenges. This in-silico study aims to enhance the understanding of optogenetic excitability in CA1 cells and to identify strategies for improving stimulation protocols.MethodsEmploying state-of-the-art computational models coupled with Monte Carlo simulated light propagation, the optogenetic excitability of four CA1 cells, two pyramidal and two interneurons, expressing ChR2(H134R) is investigated.Results and discussionThe results demonstrate that confining the opsin to specific neuronal membrane compartments significantly improves excitability. An improvement is also achieved by focusing the light beam on the most excitable cell region. Moreover, the perpendicular orientation of the optical fiber relative to the somato-dendritic axis yields superior results. Inter-cell variability is observed, highlighting the importance of considering neuron degeneracy when designing optogenetic tools. Opsin confinement to the basal dendrites of the pyramidal cells renders the neuron the most excitable. A global sensitivity analysis identified opsin location and expression level as having the greatest impact on simulation outcomes. The error reduction of simulation outcome due to coupling of neuron modeling with light propagation is shown. The results promote spatial confinement and increased opsin expression levels as important improvement strategies. On the other hand, uncertainties in these parameters limit precise determination of the irradiance thresholds. This study provides valuable insights on optogenetic excitability of CA1 cells useful for the development of improved optogenetic stimulation protocols for, for instance, TLE treatment.

【 授权许可】

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Copyright © 2023 Schoeters, Tarnaud, Weyn, Joseph, Raedt and Tanghe.