Listening to membrane potential

  • J. Kang, S. D. Kadam, J. Elmore, B. J. Sullivan, H. Valentine, A. P. Malla, M. M. Harraz, A. Rahmim, J. U. Kang, L. M. Loew, M. Baumann, A. A. Grace, A. Gjedde, E. M. Boctor, and D. F. Wong, “Transcranial photoacoustic imaging of NMDA-evoked focal circuit dynamics in rat hippocampus,” Journal of Neural Engineering 17(2), 025001, 8 Apr. 2020
  • J. Kang, H. K. Zhang, S. Kadam, J. Fedorko, H. Valentine, A. P. Malla, P. Yan, M. M. Harraz, Jin U. Kang, A. Rahmim, A. Gjedde, L. M. Loew, D. F. Wong, and E. M. Boctor, “Transcranial recording of electrophysiological neural activity in the rodent brain in vivo using functional photoacoustic imaging of near-infrared voltage-sensitive dye,” Frontiers in Neuroscience 13(579), 1-14, 9 Aug. 2019
  • [H. K. Zhang, P. Yan], J. Kang, D. Abou, H. N. D. Le, D. Thorek, J. U. Kang, A. Gjedde, A. Rahmim, D. F. Wong, L. M. Loew, E. M. Boctor, “Listening to membrane potential: photoacoustic voltage-sensitive dye recording,” Journal of Biomedical Optics22(4), 045006, 10 Apr. 2017.

Voltage-sensitive dyes (VSDs) are designed to monitor membrane potential by detecting fluores- cence changes in response to neuronal or muscle electrical activity. However, fluorescence imaging is limited by depth of penetration and high scattering losses, which leads to low sensitivity in vivo systems for external detection. By contrast, photoacoustic (PA) imaging, an emerging modality, is capable of deep tissue, noninvasive imaging by combining near-infrared light excitation and ultrasound detection. Here, we show that voltage-dependent quenching of dye fluorescence leads to a reciprocal enhancement of PA intensity. We synthesized a near-infrared photoacoustic VSD (PA-VSD), whose PA intensity change is sensitive to membrane potential. In the polarized state, this cyanine-based probe enhances PA intensity while decreasing fluorescence output in a lipid vesicle membrane model. A theoretical model accounts for how the experimental PA intensity change depends on fluorescence and absorbance properties of the dye. These results not only demonstrate PA voltage sensing but also emphasize the interplay of both fluorescence and absorbance properties in the design of optimized PA probes. Together, our results demonstrate PA sensing as a potential new modality for recording and external imaging of electrophysiological and neurochemical events in the brain.