Gold‐Nanorod‐Assisted Near‐Infrared Stimulation of Primary Auditory Neurons

Abstract

Infrared stimulation offers an alternative to electrical stimulation of neuronal tissue, with potential for direct, non-contact activation at high spatial resolution. Conventional methods of infrared neural stimulation (INS) rely on transient heating due to the absorption of relatively intense laser beams by water in the tissue. However, the water absorption also limits the depth of penetration of light in tissue. Therefore, the use of a near-infrared laser at 780 nm to stimulate cultured rat primary auditory neurons that are incubated with silica-coated gold nanorods (Au NRs) as an extrinsic absorber is investigated. The laser-induced electrical behavior of the neurons is observed using whole-cell patch clamp electrophysiology. The nanorod-treated auditory neurons (NR-ANs) show a significant increase in electrical activity compared with neurons that are incubated with non-absorbing silica-coated gold nanospheres and control neurons with no gold nanoparticles. The laser-induced heating by the nanorods is confirmed by measuring the transient temperature increase near the surface of the NR-ANs with an open pipette electrode. These findings demonstrate the potential to improve the efficiency and increase the penetration depth of INS by labeling nerves with Au NRs and then exposing them to infrared wavelengths in the water window of tissue.

Synergistic combination of near-infrared irradiation and targeted gold nanoheaters for enhanced photothermal neural stimulation

“…Illuminating gold nanorods (GNRs) at their resonant wavelengths leads to efficient light absorption and local electromagnetic field enhancement, finally realizing a plasmonic nanoheater [22][23][24]. Since plasmonic nanoheaters can efficiently elevate local temperature, INS combined with GNRs has a potential for improving an optical activation or inhibition of neuronal metabolisms [18,[24][25][26] while avoiding tissue damage by excessive heating. Previously, we presented that an optical neural stimulation using NIR light incorporating plasmonic nanoheaters injected in a proximity of neuron cells could significantly enhance the neural responses of a rat sciatic nerve in vivo [24].…”

Target structures for cochlear infrared neural stimulation

“…[1][2][3][4][5][6][7] The common underlying mechanism of infrared neural stimulation (INS) is the local heating of the target structures in the beam path. [8][9][10] Experimental results show that the temperature changes result in a depolarizing capacitive current or the activation of heat-sensitive transient receptor potential vallinioid (TRPV) channels. 11,12 Other experiments demonstrated that IR increases the intracellular calcium concentration.…”

Gold Nanorod-assisted Optical Stimulation of Neuronal Cells

“…Yong and coworkers recorded a significant increase in electrical signal activity in primary auditory neurons cultured with silica-coated Au NRs after laser irradiation of the NRs at the LSPR. The heating produced by the laser-irradiated particles was measured using patch-clamp techniques 14 . More recently, Eom et al recorded an increase in the amplitude of CNAPs after laser exposure of 3.4 × 10 9 Au NRs when continuously perfused in the vicinity of the sheath of the nerve bundle of a rat sciatic nerve 15 .…”

“…Do not add the particles for the control experiments. Note: As an alternative control, Au NPs with a well-differentiated peak absorption wavelength can be used for comparison purposes 14 . For a more consistent cell behavior, keep the cell density constant and do not modify the well surface prior to cell seeding.…”

“…Similarly, intracellular calcium transients were recorded in neuronal cells cultured with Au NRs after laser irradiation modulated with variable frequencies and pulse lengths 13 . Cell membrane depolarization was also recorded after NIR laser illumination of Au NRs in primary cultures of spiral ganglion neurons 14 . The first in vivo application with irradiated Au NRs has been demonstrated just recently.…”