Optogenetic Approaches for Controlling Seizure Activity

Tung, Jack K.; Berglund, Ken; Gross, Robert E.

doi:10.1016/j.brs.2016.06.055

Cited by 27 publications

(17 citation statements)

References 115 publications

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“…Optogenetics has shown promising results in treating rodent models of various psychiatric and neurological diseases including epilepsy (for review, Tung, Berglund, & Gross, 2016a). SSFO CS/DA , when expressed in the ventrobasal complex of the thalamus, can bidirectionally control epileptic networks and prevent seizures by switching the firing mode of thalamocortical neurons from burst firing to tonic firing (Sorokin et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Step‐function luminopsins for bimodal prolonged neuromodulation

Berglund

Fernandez

Gutekunst

et al. 2019

J of Neuroscience Research

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Although molecular tools for controlling neuronal activity by light have vastly expanded, there are still unmet needs which require development and refinement. For example, light delivery into the brain is still a major practical challenge that hinders potential translation of optogenetics in human patients. In addition, it would be advantageous to manipulate neuronal activity acutely and precisely as well as chronically and non‐invasively, using the same genetic construct in animal models. We have previously addressed these challenges by employing bioluminescence and have created a new line of opto‐chemogenetic probes termed luminopsins by fusing light‐sensing opsins with light‐emitting luciferases. In this report, we incorporated Chlamydomonas channelrhodopsin 2 with step‐function mutations as the opsin moiety in the new luminopsin fusion protein termed step‐function luminopsin (SFLMO). Bioluminescence‐induced photocurrent lasted longer than the bioluminescence signal due to very slow deactivation of the mutated channel. In addition, bioluminescence was able to activate most of the channels on the cell surface due to the extremely high light sensitivity of the channel. This efficient channel activation was partly mediated by radiationless bioluminescence resonance energy transfer due to the proximity of luciferase and opsin. To test the utility of SFLMOs in vivo, we transduced the substantia nigra unilaterally via a viral vector in male rats. Injection of the luciferase substrate as well as conventional photostimulation via fiber optics elicited circling behaviors. Thus, SFLMOs expand the current approaches for manipulation of neuronal activity in the brain and add more versatility and practicality to optogenetics in freely behaving animals.

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Section: Discussionmentioning

confidence: 99%

Step‐function luminopsins for bimodal prolonged neuromodulation

Berglund

Fernandez

Gutekunst

et al. 2019

J of Neuroscience Research

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“…Optogenetic tools (Nagel et al, 2003) have the potential to bypass many of the limitations of electrical stimulation (Delbeke et al, 2017). This technique has been validated in blind animal models of Retinitis Pigmentosa (Sahel & Roska, 2013) and is moving towards human trials for retinal prosthesis (Sahel et al, 2015;Tung et al, 2016;Sengupta et al, 2016;Barrett et al, 2016). The power of optogenetics is that specific neural sub-circuits can be targeted using gene therapy to express the light-sensitive ion channels, and high fidelity control of neural firing can be achieved.…”

Section: Electrode-to-tissue Interface Issuesmentioning

confidence: 99%

Development of visual Neuroprostheses: trends and challenges

Fernández

2018

Bioelectron Med

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Visual prostheses are implantable medical devices that are able to provide some degree of vision to individuals who are blind. This research field is a challenging subject in both ophthalmology and basic science that has progressed to a point where there are already several commercially available devices. However, at present, these devices are only able to restore a very limited vision, with relatively low spatial resolution. Furthermore, there are still many other open scientific and technical challenges that need to be solved to achieve the therapeutic benefits envisioned by these new technologies. This paper provides a brief overview of significant developments in this field and introduces some of the technical and biological challenges that still need to be overcome to optimize their therapeutic success, including long-term viability and biocompatibility of stimulating electrodes, the selection of appropriate patients for each artificial vision approach, a better understanding of brain plasticity and the development of rehabilitative strategies specifically tailored for each patient.

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“…It provides unprecedented spatial and temporal precision and opportunities for a wide range of biomedical applications. [1][2][3][4][5] It has enabled the examination of the causal roles of specific neural components in normal and dysfunctional behaviors. The past decade has witnessed an explosive development of optogenetic tools, primarily microbial rhodopsin pumps and channels.…”

Section: Introductionmentioning

confidence: 99%

Theoretical optimization of high-frequency optogenetic spiking of red-shifted very fast-Chrimson-expressing neurons

2019

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A detailed theoretical analysis and optimization of high-fidelity, high-frequency firing of the red-shifted very-fast-Chrimson (vf-Chrimson) expressing neurons is presented. A four-state model for vf-Chrimson photocycle has been formulated and incorporated in Hodgkin-Huxley and Wang-Buzsaki spiking neuron circuit models. The effect of various parameters that include irradiance, pulse width, frequency, expression level, and membrane capacitance has been studied in detail. Theoretical simulations are in excellent agreement with recently reported experimental results. The analysis and optimization bring out additional interesting features. A minimal pulse width of 1.7 ms at 23 mW∕mm 2 induces a peak photocurrent of 1250 pA. Optimal irradiance (0.1 mW∕mm 2) and pulse width (50 μs) to trigger action potential have been determined. At frequencies beyond 200 Hz, higher values of expression level and irradiance result in spike failure. Singlet and doublet spiking fidelity can be maintained up to 400 and 150 Hz, respectively. The combination of expression level and membrane capacitance is a crucial factor to achieve high-frequency firing above 500 Hz. Its optimization enables 100% spike probability of up to 1 kHz. The study is useful in designing new high-frequency optogenetic neural spiking experiments with desired spatiotemporal resolution, by providing insights into the temporal spike coding, plasticity, and curing neurodegenerative diseases.

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Optogenetic Approaches for Controlling Seizure Activity

Cited by 27 publications

References 115 publications

Step‐function luminopsins for bimodal prolonged neuromodulation

Step‐function luminopsins for bimodal prolonged neuromodulation

Development of visual Neuroprostheses: trends and challenges

Theoretical optimization of high-frequency optogenetic spiking of red-shifted very fast-Chrimson-expressing neurons

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