Despite a potential of infrared neural stimulation (INS) for modulating neural activities, INS suffers from limited light confinement and bulk tissue heating. Here, a novel methodology for an advanced optical stimulation is proposed by combining near-infrared (NIR) stimulation with gold nanorods (GNRs) targeted to neuronal cell membrane. We confirmed experimentally that in vitro and in vivo neural activation is associated with a local heat generation based on NIR stimulation and GNRs. Compared with the case of NIR stimulation without an aid of GNRs, combination with celltargeted GNRs allows photothermal stimulation with faster neural response, lower delivered energy, higher stimulation efficiency and stronger behavior change. Since the suggested method can reduce a requisite radiant exposure level and alleviate a concern of tissue damage, it is expected to open up new possibilities for applications to optical neuromodulations for diverse excitable tissues and treatments of neurological disorders. Hollenberg, M.-E. Lee, and E. Haber, "Thy-1, a novel marker for angiogenesis upregulated by inflammatory cytokines," Circ. Res. 82(8), 845-851 (1998). 37. S. Tandon, N. Kambi, and N. Jain, "Overlapping representations of the neck and whiskers in the rat motor cortex revealed by mapping at different anaesthetic depths," Eur. J. Neurosci. 27(1), 228-237 (2008). 38. M. Brecht, M. Schneider, B. Sakmann, and T. W. Margrie, "Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex," Nature 427(6976), 704-710 (2004).
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