Quantitative analysis of the optogenetic excitability of CA1 neurons.
NEURON
computational modeling
cornu ammonis
optogenetics
sensitivity analysis
tissue activation
Journal
Frontiers in computational neuroscience
ISSN: 1662-5188
Titre abrégé: Front Comput Neurosci
Pays: Switzerland
ID NLM: 101477956
Informations de publication
Date de publication:
2023
2023
Historique:
received:
26
05
2023
accepted:
27
07
2023
medline:
31
8
2023
pubmed:
31
8
2023
entrez:
31
8
2023
Statut:
epublish
Résumé
Optogenetics 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 Employing 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. The 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.
Identifiants
pubmed: 37649730
doi: 10.3389/fncom.2023.1229715
pmc: PMC10465168
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1229715Informations de copyright
Copyright © 2023 Schoeters, Tarnaud, Weyn, Joseph, Raedt and Tanghe.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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