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Theoretical analysis of low-power deep synergistic sono-optogenetic excitation of neurons by co-expressing light-sensitive and mechano-sensitive ion-channels

Year: 2025
Type: article
Abstract: The present challenge in neuroscience is to non-invasively exercise low-power and high-fidelity control of neurons situated deep inside the brain. Although, two-photon optogenetic excitation can activate neurons to millimeter depth with sub-cellular specificity and millisecond temporal resolution, it can also cause heating of the targeted tissue. On the other hand, sonogenetics can non-invasively modulate the cellular activity of neurons expressed with mechano-sensitive proteins in deeper areas of the brain with less spatial selectivity. We present a theoretical analysis of a synergistic sono-optogenetic method to overcome these limitations by co-expressing a mechano-sensitive (MscL-I92L) ion-channel with a light-sensitive (CoChR/ChroME2s/ChRmine) ion-channel in hippocampal neurons. It is shown that in the presence of low-amplitude subthreshold ultrasound pulses, the two-photon excitation threshold for neural spiking reduces drastically by 73% with MscL-I92L-CoChR (0.021 mW/µm2), 66% with MscL-I92L-ChroME2s (0.029 mW/µm2), and 64% with MscL-I92L-ChRmine (0.013 mW/µm2) at 5 Hz. It allows deeper excitation of up to 1.2 cm with MscL-I92L-ChRmine combination. The method is useful to design new experiments for low-power deep excitation of neurons and multimodal neuroprosthetic devices and circuits. A new synsonoptogenetic method is shown to drastically lower 2P excitation threshold enabling low-power deep neural activation of hippocampal neurons, expressed with ChRmine and MscL-I92L, in the presence of low-amplitude subthreshold ultrasound.
DOI: 10.1038/s42003-025-07792-8
Language: English
Open Access status: gold
Estimated APC paid: $4,190
OpenAlex ID: W4408188050
FWCI: 1.714
Cites: 119
Cited by: 5
Related to: 10