Through-scalp deep-brain stimulation in tether-free, naturally-behaving mice with widefield NIR-II illumination

Abstract

Neural modulation techniques with electricity, light and other forms of energy have enabled the deconstruction of neural circuitry. One major challenge of existing neural modulation techniques is the invasive brain implants and the permanent skull attachment of an optical fiber for modulating neural activity in the deep brain. Here we report an implant-free and tether-free optical neuromodulation technique in deep-brain regions through the intact scalp with brain-penetrant second near-infrared (NIR-II) illumination. Macromolecular infrared nanotransducers for deep-brain stimulation (MINDS) demonstrate exceptional photothermal conversion efficiency of 71% at 1064 nm, the wavelength that minimizes light attenuation by the brain in the entire 400-1700 nm spectrum. Upon widefield 1064-nm illumination >50 cm above the mouse head at a low incident power density of 10 mW/mm2, deep-brain neurons are activated by MINDS-sensitized TRPV1 channels with minimal thermal damage. Our approach could open opportunities for simultaneous neuromodulation of multiple socially interacting animals by remotely irradiating NIR-II light to stimulate each subject individually.

Shedding light on neurons: optical approaches for neuromodulation

“…[ 24 ], the data in (d) are reproduced from ref. [ 19 ] and the data in (e) and (f) are calculated from Equations 7 and 9 , respectively.…”

“…It is noteworthy that the maximum penetration depth is found at 1070 nm, which is close to the operation wavelength of the Nd:YAG laser, 1064 nm. The wide availability of the Nd:YAG laser and the maximum penetration depth of light near its operation wavelength in the brain thus make this wavelength region (1050–1100 nm) attractive for deep-brain neuromodulation [ 19 ]. As a comparison, we estimate the percentage of photons reaching a depth of 4 mm in the brain in Fig.…”

Nanotransducers for wireless neuromodulation

“…Lyu et al 42 Review semiconducting polymer nanobioconjugates, macromolecular infrared nanotransducers for deep brain stimulation have been demonstrated to enable through-scalp neuromodulation in freely moving mice. 100 Owing to the minimized tissue attenuation of 1064-nm NIR-II irradiation, macromolecular infrared nanotransducers for deep-brain stimulation (MINDS) have enabled neuromodulation in the motor cortex and ventral tegmental area of naturally behaving mice with wide-field NIR-II illumination at a low power density, in contrast to a fiber-tethered interface required for conventional optogenetic neuromodulation. This approach can remotely apply light to stimulate individual animals in the same arena, such as the IntelliCage, thus may enable simultaneous neuromodulation of multiple socially interacting animals.…”

Material Engineering Platform for Next Generation of Neurobiological Interfaces

“…6 The characteristic emission spectra and the energy conversion efficiency of the upconversion nanoparticles can be customized by turning the core−shell structures during synthesis. In organic macromolecules that convert NIR into heat dissipation and consequently activate genetically modified thermal-sensitive cells, 7 design of the macromolecule structure determines the photothermal efficiency, water-based processability and biocompatibility for in vivo applications.…”