Subsecond multichannel magnetic control of select neural circuits in freely moving flies.

Precisely timed activation of genetically targeted cells is a powerful tool for the study of neural circuits and control of cell-based therapies. Magnetic control of cell activity, or 'magnetogenetics', using magnetic nanoparticle heating of temperature-sensitive ion channels enables remote, non-invasive activation of neurons for deep-tissue applications and freely behaving animal studies. However, the in vivo response time of thermal magnetogenetics is currently tens of seconds, which prevents precise temporal modulation of neural activity. Moreover, magnetogenetics has yet to achieve in vivo multiplexed stimulation of different groups of neurons. Here we produce subsecond behavioural responses in Drosophila melanogaster by combining magnetic nanoparticles with a rate-sensitive thermoreceptor (TRPA1-A). Furthermore, by tuning magnetic nanoparticles to respond to different magnetic field strengths and frequencies, we achieve subsecond, multichannel stimulation. These results bring magnetogenetics closer to the temporal resolution and multiplexed stimulation possible with optogenetics while maintaining the minimal invasiveness and deep-tissue stimulation possible only by magnetic control.

Multichannel power electronics and magnetic nanoparticles for selective thermal magnetogenetics.

Objective.We present a combination of a power electronics system and magnetic nanoparticles that enable frequency-multiplexed magnetothermal-neurostimulation with rapid channel switching between three independent channels spanning a wide frequency range.Approach.The electronics system generates alternating magnetic field spanning 50 kHz to 5 MHz in the same coil by combining silicon (Si) and gallium-nitride (GaN) transistors to resolve the high spread of coil impedance and current required throughout the wide bandwidth. The system drives a liquid-cooled field coil via capacitor banks, forming three series resonance channels which are multiplexed using high-voltage contactors. We characterized the system by the output channels' frequencies, field strength, and switching time, as well as the system's overall operation stability. Using different frequency-amplitude combinations of the magnetic field to target specific magnetic nanoparticles with different coercivity, we demonstrate actuation of iron oxide nanoparticles in all three channels, including a novel nanoparticle composition responding to magnetic fields in the megahertz range.Main results.The system achieved the desired target field strengths for three frequency channels, with switching speed between channels on the order of milliseconds. Specific absorption rate measurements and infrared thermal imaging performed with three types of magnetic nanoparticles demonstrated selective heating and validated the system's intended use.Significance.The system uses a hybrid of Si and GaN transistors in bridge configuration instead of conventional amplifier circuit concepts to drive the magnetic field coil and contactors for fast switching between different capacitor banks. Series-resonance circuits ensure a high output quality while keeping the system efficient. This approach could significantly improve the speed and flexibility of frequency-multiplexed nanoparticle actuation, such as magnetogenetic neurostimulation, and thus provide the technical means for selective stimulation below the magnetic field's fundamental spatial focality limits.

Biohybrid approaches to interface with the nervous system: the best of both worlds.

Synthetic materials and devices that interact with light, ultrasound, or magnetic fields can be used to modulate neural activity with high spatial and temporal precision; however, these approaches often lack the ability to target genetically defined cell types and signaling pathways. Genetically encoded proteins can be expressed to modify the host tissue and provide cellular and molecular specificity, but compared to synthetic materials, these proteins often interact weakly with externally applied energy sources. Synthetic materials can respond to optical, acoustic, and magnetic stimuli to focus, convert, and amplify forms of energy to ones that are more accessible to engineered cells and proteins. By combining the devices, synthetic materials, and genetically encoded proteins or cells, researchers can gain the ability to interface with the nervous system with improved spatiotemporal, cell-type and molecular precision. Here we review recent advances in these 'biohybrid' approaches that use optical, acoustic, and magnetic energy sources.