Deconvolving Neuronal Ensembles from Macroscopic Neural Activities in Voltage-Sensitive Dye Image Streams on Mouse Cerebrum Slices

Authors

  • Karin Horiuchi Dept. of Electrical Engineering, National Institute of Technology Nara College, Nara, Japan https://orcid.org/0009-0003-2585-1004
  • Santa Fukuda Dept. Information Engineering, Grad. Engineering, Mie University, Mie, Japan https://orcid.org/0000-0001-6932-6875
  • Masahiro Ohtani Dept. of Electrical Engineering, National Institute of Technology Nara College, Nara, Japan
  • Yuki Hayashida Dept. Information Engineering, Grad. Engineering, Mie University, Mie, Japan https://orcid.org/0000-0002-1523-5385

DOI:

https://doi.org/10.22452/mjs.vol45sp2.4

Keywords:

Visual prosthesis, Neuronal ensemble, Voltage-sensitive dye imaging, Spatio-temporal cross-correlation analyses

Abstract

Previous clinical trials have demonstrated that electrical microstimulation delivered within the primary visual cortex (V1) in human subjects with acquired blindness can evoke focal light sensations in their visual fields, supporting the feasibility of intracortical visual prostheses. Our previous animal studies using voltage-sensitive dye (VSD) imaging examined the spatiotemporal patterns of cortical neural activity in response to electrical current-pulse stimuli, varying stimulus parameters to optimize stimulation design. These studies revealed specific relationships between stimulus parameters and neural responses at millisecond temporal resolution and submillimeter spatial scales. However, as VSD images typically represent voltage changes across all cytoplasmic membranes of cells responding to stimuli, activities of individual neuron populations and their functional connections are obscured by the macroscopic responses. This study aims to investigate stimulus-induced neuronal activities at a finer spatial resolution by employing image processing techniques. Specifically, spatial and temporal cross-correlation analyses were applied to VSD image streams to identify spatially distinguishable patterns of pixel clusters exhibiting temporally correlated VSD signals. In certain cases, these neuronal ensembles, each smaller than 100 micrometers in diameter, displayed time-fixed correlation in membrane voltage change, suggesting functional connectivity between them. The image processing method demonstrates the potential of separating distinct activities of cortical neuronal ensembles from macroscopic VSD imaging data, offering a valuable tool for detailed studies of stimulus-induced network dynamics and, in turn, optimizing stimuli for visual prostheses.

References

Benisty H., Song A., Mishne G., Charles A. S. (2022) Review of data processing of functional optical microscopy for neuroscience, Neuro-photonics, 9 (4): 041402 (32 pp.).

Chen X., Wang F., Fernández E., Roelfsema P. R. (2020) Shape perception via a high-channel-count neuroprosthesis in monkey visual cortex, Science 370 (6521): 1191-1196.

Fehérvári T. D., Okazaki Y., Sawai H., Yagi T. (2015) In vivo voltage-sensitive dye study of lateral spreading of cortical activity in mouse primary visual cortex induced by a current impulse, PLoS One 10 (7): e0133853 (24 pp.).

Fernández E., Alfaro A., Soto-Sánchez C., Gonzalez-Lopez P., Lozano A. M., Peña S., Grima M.D., Rodil A., Gómez B., Chen X., Roelfsema P. R., Rolston J. D., Davis T. S., Normann R. A. (2021) Visual percepts evoked with an intracortical 96-channel microelec-trode array inserted in human occipital cortex, J. Clin. Invest. 131 (23): e151331 (15 pp.).

Fukuda S., Nomoto T., Yoshida K., Hayashida Y., Yagi T. (2021) Accumulation of non-synaptic and synaptic excitations induced by microstimulation pulses in the mouse visual cortex layer II/III, 2021 43rd Ann. Int’l Conf. I.E.E.E. Med. Biol. Soc.: 5152.

Fukuda S., Yoshida K., Nomoto T., Yagi T., Hayashida Y. (2022) Use-dependent inactivation of the mouse visual cortex in response to microstimulation train, 2022 E-Health Bioeng. Conf.: 1-4.

Hayashida Y., Takeuchi K., Ishikawa N., Okazaki Y., Fehérvári T. D., Tanaka H., Yagi T. (2014) Voltage-sensitive dye imaging of the visual cortices responding to electrical pulses at different intervals in mice in vivo, 2014 36th Ann. Int’l Conf. I.E.E.E. Med. Biol. Soc.: 402-405.

Hayashida Y., Kameda S., Umehira Y., Ishikawa S., Yagi T. (2022) Multichannel stimulation module as a tool for animal studies on cortical neural pros-theses, Front. Med. Technol. 4: 927851 (21 pp.).

Miyamoto S., Suematsu N., Umehira Y., Hayashida Y., Yagi T. (2017) Age-related changes in the spatiotemporal responses to electrical stimulation in the visual cortex of rats with progressive vision loss, Sci. Rep. 7(1): 14165 (13 pp.).

Nomoto T., Tanaka Y., Hayashida Y., Yagi T. (2017) Imaging of population spikes induced by repetitive stimulus pulses in mouse cerebral slices in vitro, 2017 39th Ann. Int’l Conf. I.E.E.E. Med. Biol. Soc.: 1109.

Schmidt E. M., Bak M. J., F T Hambrecht, C V Kufta, D K O'Rourke, P Vallabhanath (1996) Feasibility of a visual prosthesis for the blind based on intracortical microstimulation of the visual cortex, Brain 119 (2): 507-522.

Tanaka Y., Nomoto T., Shiki T., Sakata Y., Shimada Y., Hayashida Y., Yagi T. (2019) Focal activation of neuronal circuits induced by microstimulation in the visual cortex, J. Neural Eng. 16 (3): 036007 (17 pp.).

Xie M. E., Adam Y., Fan L. Z., Böhm U. L., Kinsella I., Zhou D., Rozsa M., Singh A., Svoboda K., Paninski L., Cohen A. E. (2021) High-fidelity estimates of spikes and subthreshold waveforms from 1-photon voltage imaging in vivo, Cell Reports 35(1): 108954 (15 pp.).

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Published

15-11-2026