To understand the mechanism underlying the function and dynamics of nervous system, it is essential to develop the technique capable of modulating and recording a diversity of signals employed by neuron. However, current approaches are limited in terms of effectiveness, side effects, or mechanical invasiveness due to its bulky body. Consequently, there is a need for new biocompatible materials with multi-modality which allow for minimally invasive manipulation and the specific control of neural circuits. As a solution, we developed the nanoparticle-based magneto-thermal/mechanical/chemical technique for wireless deep brain stimulation. Since biological tissues exhibit negligible magnetic permeability and low conductivity, magnetic fields can penetrate deep into the body with no attenuation, which helps the interrogation with neural circuits across their diverse signaling modalities. Beyond these approaches, we are interested in various nano-materials as a transducers for specific neural control, for example, from piezoelectric nanoparticles to metal nanowire/rods.
R. Chen, P. Anikeeva et al., Science (2015)
Wireless Neural Stimulation with Magnetic Nanoparticles through Thermogenetics. (a) Experimental scheme for Wireless switch for controlled magnetothermal membrane depolarization of TRPV1+ cells (TRPV1: thermally sensitive channel). Magnetic field stimulation (“Field ON”) of TRPV1 from Magnetic nano particle (MNP) heating is visualized by gCaMP6s fluorescence changes. (b) Transmission electron micrographs of MNPs: as-synthesized and after surface modification with a 2-nm PEG shell. (c) Color maps of fluorescence intensity changes (neuron firing) for TRPV1– and TRPV1+ HEK293FT cells before and during magnetic field stimulus. (d) In vivo experimental scheme for brain stmiulation through magneto-thermogenetics. Confocal image of a coronal slice representative of the TRPV1-p2A-mCherry expression profile in the VTA.
S. Rao, S. Park, P. Anikeeva et al., Nature Nanotechnology (2019)
Magnetic Way to Control the Chemical Releases for Neural Stimulation (a) Experimental scheme of alternating magnetic field (AMF)-triggered artificial chemical payload (CNO for DREADD) release from the magneto-liposomes. (b) Transmission electron microscope (TEM) images and the size distributions of the magnetic nanoparticles (MNPs) before (I) and after (II) encapsulation into the magneto-liposomes, and the magnetoliposomes after exposure to 40 s of AMF (III). (c) Confocal images of the primary hippocampal neurons expressing hSyn::hM3D(Gq)-mCherry (for expression of channels activated by artificial chemical) and hSyn-GCaMP6s (genetically-encoded calcium indicator, neural firing indicator). (d) Experimental timeline for the viral gene delivery, magnetoliposome injection, and AMF stimulation. Inset: A confocal image of the expression of hM3D(Gq)-mCherry in the mouse VTA. (e) the percentages of c-fos (neural activity marker) expressing (c-fos+) neurons in the VTA and NAc of mice exposed to AMF (AMF+), injected with CNO-loaded magnetoliposomes (CNO+) and expressing hM3D(Gq) (hM3D(Gq)+). Increased c-fos expression is observed following chemomagnetic treatment.