Scalable approaches to modulate neural activity during complex behaviors are essential to basic study of normal and aberrant brain function. Here we aim to develop a wireless magnetomechanical neuromodulation technique suitable for remote excitation of genetically identifiable neuronal populations. This approach will rely on the ability of anisotropic synthetic magnetic nanodiscs to transduce torques to cell membranes in weak slow-varying magnetic fields. Our preliminary findings indicate that weak magnetomechanical torques robustly induce activity in sensory mechanoreceptive neurons. These observations will be extended first to magnetomechanical neuromodulation of genetically specified brain neurons targeted with nanodiscs via SNAP-tag or nanobody- based strategies. Our approach will further be refined by sensitizing specific neurons to mechanical stimuli via expression of a mechanosensitive cation channel TRPV4 (transient receptor potential vanilloid family member 4). Unlike magnetothermal techniques that rely on heat dissipated by isotropic magnetic nanoparticles in high- frequency alternating magnetic fields, magnetomechanical approach can be implemented with off-the-shelf low- power electronics and is readily scalable to volumes necessary to conduct behavioral assays in rodents and neuromodulation experiments in larger models including future studies in humans. We will evaluate our proposed targeted magnetomechanical neuromodulation approach by investigating its ability to shape dopamine- dependent behaviors in a mouse model of reward and motivation processing.
This project will demonstrate a scalable remote magnetomechanical technique to modulate neural activity during complex behaviors. We will apply this technique to interrogate mid-brain reward circuits in freely moving untethered subjects. Dopamine-dependent reward and motivation processing is disrupted in mental conditions including addiction and depression, and our technique may help advance understanding and future treatment of these disorders.
