Single-Cell Photothermal Neuromodulation for Functional Mapping of Neural Networks

Photothermal neuromodulation is one of the emerging technologies being developed for neuroscience studies because it can provide minimally invasive control of neural activity in the deep brain with submillimeter precision. However, single-cell modulation without genetic modification still remains a challenge, hindering its path to broad applications. Here, we introduce a nanoplasmonic approach to inhibit single-neural activity with high temporal resolution. Low-intensity near-infrared light was focused at the single cell size on a gold-nanorod-integrated microelectrode array platform, generating a photothermal effect underneath a target neuron for photothermal stimulation. We found that the photothermal stimulation modulates the spontaneous activity of a target neuron in an inhibitory manner. Single neuron inhibition was fast and highly reliable without thermal damage, and it can induce changes in network firing patterns, potentially suggesting their application for in vivo circuit modulation and functional connectomes.