Biophysical Mechanisms of Transient Optical Stimulation of Peripheral Nerve

Abstract

A new method for in vivo neural activation using low-intensity, pulsed infrared light exhibits advantages over standard electrical means by providing contact-free, spatially selective, artifact-free stimulation. Here we investigate the biophysical mechanism underlying this phenomenon by careful examination of possible photobiological effects after absorption-driven light-tissue interaction. The rat sciatic nerve preparation was stimulated in vivo with a Holmium:yttrium aluminum garnet laser (2.12 microm), free electron laser (2.1 microm), alexandrite laser (750 nm), and prototype solid-state laser nerve stimulator (1.87 microm). We systematically determined relative contributions from a list of plausible interaction types resulting in optical stimulation, including thermal, pressure, electric field, and photochemical effects. Collectively, the results support our hypothesis that direct neural activation with pulsed laser light is induced by a thermal transient. We then present data that characterize and quantify the spatial and temporal nature of this required temperature rise, including a measured surface temperature change required for stimulation of the peripheral nerve (6 degrees C-10 degrees C). This interaction is a photothermal effect from moderate, transient tissue heating, a temporally and spatially mediated temperature gradient at the axon level (3.8 degrees C-6.4 degrees C), resulting in direct or indirect activation of transmembrane ion channels causing action potential generation.

Thermal Transients Excite Neurons through Universal Intramembrane Mechanoelectrical Effects

“…This study explored the effects of temperature changes on membrane capacitance and its associated currents in a joint attempt to clarify the experimental results of a key recent study [16] and to pave the way towards predictive modeling of INS [2][3][4][5][6][7][8][9][10][11][12][13][14][15] and other thermal neurostimulation techniques [18][19][20], which could potentially facilitate the development of more advanced and multimodal methods for neural circuit control. Another key motivation to pursue this problem came from our noting the very similar temperature-related capacitance rates of change observed in very different model systems [ Fig.…”

“…A multitude of INS-related studies explored the ability of short-wave infrared (IR) pulses to stimulate neural structures including peripheral [3,4] and cranial nerves [5][6][7][8][9][10], retinal and cortical neurons [10][11][12], as well as cardiomyocytes [13,14]. It is stipulated that the INS phenomenon is mediated by temperature transients induced by IR absorption [15][16][17]; such transients can alternatively be induced using other forms of photoabsorption [18][19][20], or potentially by any other physical form of thermal neurostimulation that can be driven rapidly enough [21,22]. Shapiro et al [16] showed that these rapid temperature variations are directly accompanied by changes in the cell membrane's capacitance and resulting displacement currents which are unrelated to specific ionic channels; their findings on the thermal capacitance increase have been supported by experiments from several additional groups [19,20,[23][24][25].…”

Photogeneration of membrane potential hyperpolarization and depolarization in non-excitable cells

“…In 2005, Fein et al also observed membrane potential depolarization and resistance decrease following femtosecond laser disruption of the cellular plasma membrane (Fein and Terasaki 2005). More recently, a study of membrane potential changes by thermal eVects produced by mid-infrared photons showed that thermal eVects can aVect the membrane potential if the temperature rise is more than a few degrees (Wells et al 2007). Previous calculations for our optical system (Iwanaga et al 2006) which estimated a temperature rise of less than 1 degree, together with the large drop in observed membrane resistance indicates that the eVect of the laser is to create a transient hole in the membrane.…”

“…These advantages have been used to carry out novel experiments in cells such as generation of intracellular Ca 2+ waves (Smith et al 2001), dissection of intracellular chromosomes (König et al 1999), as well as inducing action potentials in neurons (Hirase et al 2002). While similar eVects have been produced using diVerent laser sources (Uzdensky and Savransky 1997;Wells et al 2007), the merits of femtosecond laser irradiations are being seen in the emergence of new applications which exploit the particular properties of ultrashort pulsewidths and near-infrared wavelengths. Although such applications are now emerging, the use of femtosecond laser illumination to provoke biological reactions in cells is in part limited by the incomplete understanding of the cellular response to high intensity light.…”

Spinal Cord Injury: Present and Future Therapeutic Devices and Prostheses

“…Light has been tested as a peripheral nerve stimulation device. 76,77 The packaging and clinical use remain unclear, but this method under development requires no special transfection or chromophore and channel insertions. Specificity of fascicle targeting within a nerve with such stimulation remains to be developed.…”