Neuronal photoactivation through second-harmonic near-infrared absorption by gold nanoparticles

Optical activation of neurons requires genetic manipulation or the use of chemical photoactivators with undesirable side effects. As a solution to these disadvantages, here, we demonstrate optically evoked neuronal activity in mouse cortical neurons in acute slices and in vivo by nonlinear excitation of gold nanoparticles. In addition, we use this approach to stimulate individual epitheliomuscular cells and evoke body contractions in Hydra vulgaris. To achieve this, we use a low-power pulsed near-infrared excitation at the double-wavelength of the plasmon resonance of gold nanoparticles, which enables optical sectioning and allows for high spatial precision and large penetration depth. The effect is explained by second-harmonic Mie scattering, demonstrating light absorption by a second-order nonlinear process, which enables photothermal stimulation of the cells. Our approach also minimizes photodamage, demonstrating a major advancement towards precise and harmless photoactivation for neuroscience and human therapeutics.