Mid-Infrared Light Exhibits Tissue-Specific Transmittance and Modulates Neural Signal Conduction Along Axons.

Non-invasive infrared (IR) modulation requires IR photons to penetrate multi-layered cranial barriers, including skin, skull bone, and dura mater. However, the wavelength-dependent transmittance profiles and the modulatory effect of IR light on neural signals remain poorly understood. Using synchrotron radiation Fourier-transform infrared (SR-FTIR) microspectroscopy, we systematically mapped transmittance spectra of freshly isolated cranial tissue layers and brain tissues (gray matter and white matter) obtained from adult mice. The viability of brain tissue was maintained through microfluidic and oxygenated artificial cerebrospinal fluid (ACSF) perfusion during spectral acquisition. We identified two IR windows with relatively high transmittance through cranial tissues: a near-infrared (NIR) window (wavelength: 1.5-3.0 μm) and a mid-infrared (MIR) window (3.5-6.0 μm). Notably, the MIR sub-band ranging from 5.2 to 5.7 μm exhibited a relatively higher transmittance through neural tissue, particularly in axon bundles, compared to the surrounding bath solution. Further electrophysiological experiments revealed that MIR with a wavelength of 5.6 μm substantially decreased the amplitude and duration of both somatic and axonal action potentials, while simultaneously facilitating their conduction velocity along both myelinated and unmyelinated axons. Together, these results identify specific IR bands that can penetrate the cranial tissue layers and reveal a wavelength-specific modulation of neural signals, providing a promising non-invasive strategy for IR neuromodulation.