Optogenetics: Keep Interpretations Light

Bernard, Christophe

doi:10.1523/eneuro.0091-20.2020

Cited by 14 publications

(7 citation statements)

References 15 publications

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“…This opsin enables a noninvasive light‐induced stimulation of neurons deep within the brain when an optical fiber is placed just above the brain surface, thus, facilitating research in large brain regions or large‐brained animals (Yizhar, Fenno, Prigge, et al., 2011). An important issue associated with optogenetics is postinhibitory rebound firing influencing the clarity of the ultimate effect of opsin activation (Bernard, 2020). Indeed, due to this phenomenon, inhibited cells may exhibit a markedly synchronized firing upon cessation of light activation.…”

Section: Discussionmentioning

confidence: 99%

Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review

El Hajj,

Al Sagheer,

Ballout

2024

J of Neuroscience Research

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Neurodegenerative diseases are progressive disorders characterized by synaptic loss and neuronal death. Optogenetics combines optical and genetic methods to control the activity of specific cell types. The efficacy of this approach in neurodegenerative diseases has been investigated in many reviews, however, none of them tackled it systematically. Our study aimed to review systematically the findings of optogenetics and its potential applications in animal models of chronic neurodegenerative diseases and compare it with deep brain stimulation and designer receptors exclusively activated by designer drugs techniques. The search strategy was performed based on the PRISMA guidelines and the risk of bias was assessed following the Systematic Review Centre for Laboratory Animal Experimentation tool. A total of 247 articles were found, of which 53 were suitable for the qualitative analysis. Our data revealed that optogenetic manipulation of distinct neurons in the brain is efficient in rescuing memory impairment, alleviating neuroinflammation, and reducing plaque pathology in Alzheimer's disease. Similarly, this technique shows an advanced understanding of the contribution of various neurons involved in the basal ganglia pathways with Parkinson's disease motor symptoms and pathology. However, the optogenetic application using animal models of Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis was limited. Optogenetics is a promising technique that enhanced our knowledge in the research of neurodegenerative diseases and addressed potential therapeutic solutions for managing these diseases' symptoms and delaying their progression. Nevertheless, advanced investigations should be considered to improve optogenetic tools' efficacy and safety to pave the way for their translatability to the clinic.

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Section: Discussionmentioning

confidence: 99%

Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review

El Hajj,

Al Sagheer,

Ballout

2024

J of Neuroscience Research

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“…However, whether such a mechanism would exactly compensate for the reduction in PV-IN-mediated IPSCs in a slice is debatable and cannot be resolved by using chemogenetic strategies which would potentially suffer from similar network level changes. The inability of optical/chemogenetic silencing to disambiguate direct from circuit-effects need to be considered while using cell-specific silencing strategies (Bernard, 2020). Interestingly, a prior study found limited contribution of PV-INs to action potential independent miniature IPSCs in GCs (Goswami et al, 2012) and mutations impairing PV expression were shown to alter GC evoked IPSCs without impacting sIPSC frequency (Lucas et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Differential Activity-Dependent Increase in Synaptic Inhibition and Parvalbumin Interneuron Recruitment in Dentate Granule Cells and Semilunar Granule Cells

Afrasiabi

Gupta

et al. 2022

J. Neurosci.

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Strong inhibitory synaptic gating of dentate gyrus granule cells (GCs), attributed largely to fast-spiking parvalbumin interneurons (PV-INs), is essential to maintain sparse network activity needed for dentate dependent behaviors. However, the contribution of PV-INs to basal and input-driven sustained synaptic inhibition in GCs and semilunar granule cells (SGCs), a sparse morphologically distinct dentate projection neuron subtype, is currently unknown. In studies conducted in hippocampal slices from mice, we find that although basal IPSCs are more frequent in SGCs and optical activation of PV-INs reliably elicited IPSCs in both GCs and SGCs, optical suppression of PV-INs failed to reduce IPSC frequency in either cell type. Amplitude and kinetics of IPSCs evoked by perforant path (PP) activation were not different between GCs and SGCs. However, the robust increase in sustained polysynaptic IPSCs elicited by paired afferent stimulation was lower in SGCs than in simultaneously recorded GCs. Optical suppression of PV-IN selectively reduced sustained IPSCs in SGCs but not in GCs. These results demonstrate that PV-INs, while contributing minimally to basal synaptic inhibition in both GCs and SGCs in slices, mediate sustained feedback inhibition selectively in SGCs. The temporally selective blunting of activity-driven sustained inhibitory gating of SGCs could support their preferential and persistent recruitment during behavioral tasks.

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“…However, as is the case with any newly developed methodology, one must also be wary of the caveats. Recently, Christophe Bernard reviewed some confounding factors that should be taken into account when interpreting optogenetic effects (Bernard, 2020), such as brain dynamics, cell dynamics, possible perturbations by inserted channelrhodopsins, possibility of the light perturbing native proteins and modifications triggered by the viral vectors. We have to always be aware of what this means for data interpretation.…”

Section: Discussionmentioning

confidence: 99%

Combining magnetic resonance imaging with readout and/or perturbation of neural activity in animal models: Advantages and pitfalls

et al. 2022

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One of the main challenges in brain research is to link all aspects of brain function: on a cellular, systemic, and functional level. Multimodal neuroimaging methodology provides a continuously evolving platform. Being able to combine calcium imaging, optogenetics, electrophysiology, chemogenetics, and functional magnetic resonance imaging (fMRI) as part of the numerous efforts on brain functional mapping, we have a unique opportunity to better understand brain function. This review will focus on the developments in application of these tools within fMRI studies and highlight the challenges and choices neurosciences face when designing multimodal experiments.

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Optogenetics: Keep Interpretations Light

Cited by 14 publications

References 15 publications

Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review

Optogenetics in chronic neurodegenerative diseases, controlling the brain with light: A systematic review

Differential Activity-Dependent Increase in Synaptic Inhibition and Parvalbumin Interneuron Recruitment in Dentate Granule Cells and Semilunar Granule Cells

Combining magnetic resonance imaging with readout and/or perturbation of neural activity in animal models: Advantages and pitfalls

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