Dataset Information

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

ABSTRACT: 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/mm2 induces a peak photocurrent of 1250 pA. Optimal irradiance ( 0.1??mW/mm2 ) and pulse width ( 50???s ) 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.

SUBMITTER: Gupta N

PROVIDER: S-EPMC6458485 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Gupta Neha N Bansal Himanshu H Roy Sukhdev S

Neurophotonics 20190411 2

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 ...[more]

PMID: 31001567

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Project description:BackgroundHuman African trypanosomiasis is caused by infection with parasites of the Trypanosoma brucei species complex, and threatens over 70 million people in sub-Saharan Africa. Development of new drugs is hampered by the limitations of current rodent models, particularly for stage II infections, which occur once parasites have accessed the CNS. Bioluminescence imaging of pathogens expressing firefly luciferase (emission maximum 562 nm) has been adopted in a number of in vivo models of disease to monitor dissemination, drug-treatment and the role of immune responses. However, lack of sensitivity in detecting deep tissue bioluminescence at wavelengths below 600 nm has restricted the wide-spread use of in vivo imaging to investigate infections with T. brucei and other trypanosomatids.Methodology/principal findingsHere, we report a system that allows the detection of fewer than 100 bioluminescent T. brucei parasites in a murine model. As a reporter, we used a codon-optimised red-shifted Photinus pyralis luciferase (PpyRE9H) with a peak emission of 617 nm. Maximal expression was obtained following targeted integration of the gene, flanked by an upstream 5'-variant surface glycoprotein untranslated region (UTR) and a downstream 3'-tubulin UTR, into a T. brucei ribosomal DNA locus. Expression was stable in the absence of selective drug for at least 3 months and was not associated with detectable phenotypic changes. Parasite dissemination and drug efficacy could be monitored in real time, and brain infections were readily detectable. The level of sensitivity in vivo was significantly greater than achievable with a yellow firefly luciferase reporter.Conclusions/significanceThe optimised bioluminescent reporter line described here will significantly enhance the application of in vivo imaging to study stage II African trypanosomiasis in murine models. The greatly increased sensitivity provides a new framework for investigating host-parasite relationships, particularly in the context of CNS infections. It should be ideally suited to drug evaluation programmes.

Dataset Information

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

Publications

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

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