An advanced optical activation of neural tissues is demonstrated using pulsed infrared light and plasmonic gold nanorods. Photothermal effect localized in plasma membrane triggers action potentials of in vivo neural tissues. Compared with conventional infrared stimulation, the suggested method can increase a neural responsivity and lower a threshold stimulation level significantly, thereby reducing a requisite radiant exposure and the concern of tissue damage.

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).

Over the past decade, optical methods have emerged for modulating brain functions as an alternative to electrical stimulation. Among various optical techniques, infrared neural stimulation has been effective via a thermal mechanism enabling focused and noninvasive stimulation without any genetic manipulation, but it results in bulk heating of neural tissue. Recently, it has been shown that neural cells can be activated more efficiently by pulsed near-infrared (NIR) light delivered to gold nanorods (GNRs) near the neural cells. Despite its potential, however, the biophysical mechanism underlying this GNR-enhanced NIR stimulation has not been clearly explained yet. Here, we propose an integrative and quantitative model to elucidate the mechanism by modeling heat generated from interaction between NIR light and GNRs, the temperature-dependent ion channels (transient receptor potential vanilloid 1; TRPV1) in the neuronal membrane, and a heat-induced capacitive current through the membrane. Our results show that NIR pulses induce abrupt temperature elevation near the neuronal membrane and lead to both the TRPV1-channel and capacitive currents. Both current sources synergistically increase the membrane potential and elicit an action potential, and which mechanism is dominant depends on conditions such as the laser pulse duration and TRPV1 channel density. Although the TRPV1 mechanism dominates in most cases we tested, the capacitive current makes a larger contribution when a very short laser pulse is illuminated on neural cells with relatively low TRPV1 channel densities.

Retinal prostheses are implantable devices that aim to restore the vision of blind patients suffering from retinal degeneration, mainly by artificially stimulating the remaining retinal neurons. Some retinal prostheses have successfully reached the stage of clinical trials; however, these devices can only restore vision partially and remain insufficient to enable patients to conduct everyday life independently. The visual acuity of the artificial vision is limited by various factors from both engineering and physiological perspectives. To overcome those issues and further enhance the visual resolution of retinal prostheses, a variety of retinal prosthetic approaches have been proposed, based on optimization of the geometries of electrode arrays and stimulation pulse parameters. Other retinal stimulation modalities such as optics, ultrasound, and magnetics have also been utilized to address the limitations in conventional electrical stimulation. Although none of these approaches have been clinically proven to fully restore the function of a degenerated retina, the extensive efforts made in this field have demonstrated a series of encouraging findings for the next generation of retinal prostheses, and these could potentially enhance the visual acuity of retinal prostheses. In this article, a comprehensive and up-to-date overview of retinal prosthetic strategies is provided, with a specific focus on a quantitative assessment of visual acuity results from various retinal stimulation technologies. The aim is to highlight future directions toward high-resolution retinal prostheses.