Neuromodulation technologies are crucial for investigating neuronal connectivity and brain function. Magnetic neuromodulation offers wireless and remote deep brain stimulations that are lacking in optogenetic- and wired-electrode-based tools. However, due to the limited understanding of working principles and poorly designed magnetic operating systems, earlier magnetic approaches have yet to be utilized. Furthermore, despite its importance in neuroscience research, cell-type-specific magnetic neuromodulation has remained elusive. Here we present a nanomaterials-based magnetogenetic toolbox, in conjunction with Cre-loxP technology, to selectively activate genetically encoded Piezo1 ion channels in targeted neuronal populations via torque generated by the nanomagnetic actuators in vitro and in vivo. We demonstrate this cell-type-targeting magnetic approach for remote and spatiotemporal precise control of deep brain neural activity in multiple behavioural models, such as bidirectional feeding control, long-term neuromodulation for weight control in obese mice and wireless modulation of social behaviours in multiple mice in the same physical space. Our study demonstrates the potential of cell-type-specific magnetogenetics as an effective and reliable research tool for life sciences, especially in wireless, long-term and freely behaving animals. Minimally invasive cellular-level target-specific neuromodulation is needed to decipher brain function and neural circuitry. Here nano-magnetogenetics using magnetic force actuating nanoparticles has been reported, enabling wireless and remote stimulation of targeted deep brain neurons in freely behaving animals.
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Ushio-Fukai and Dr. Tohru Fukai reported in Nature Cell Biology that ROS rapidly modifies CTR1, a cell surface receptor that usually allows essential mineral copper to enter the interior, where its tasks include aiding angiogenesis. Modification of CTR1 prompts it to bind to the VEGF receptor, VEGFR2, also on the cell surface, and the united pair dives inside. This movement enables the sustained VEGFR2 signaling that is essential for making new blood vessels. The researchers also have evidence that Drp1 is also modified by ROS, prompting it to move from a passive state in the fluid part of the cell, or cytosol, to the mitochondria where it still promotes fission, which also produces the powerful hydrogen peroxide ROS. She says that active mitochondria are high users of oxygen and therefore, like NADPH oxidase, high producers of ROS in endothelial cells. The researchers showed that the ROS generated by mitochondria in turn activates AMPK, a key enzyme for regulating energy levels in cells and known to use glucose to rapidly generate enough energy to support important biological work such as making new blood vessels.