Magnetogenetics inspired by animal Magnetoreception: ΔTRPV4MagR as a novel magnetogenetic actuator enabling remote neuromodulation of brain circuits

Upon magnetic stimulation, ΔTRPV4^MagR expressing HEK293T cells exhibited calcium influx in a strength-dependent manner examined by the Fluo-4 experiment. While under 40 mT, 0.1 Hz magnetic stimulation, ΔTRPV4^MagR induced calcium influx was more potent than Magneto 2.0 (ΔTRPV4^Ferritin). Interestingly, the MagR of pigeon (cMagR) or human origin has superior magnetic sensitivity to that of drosophila origin (dMagR). Moreover, for the freely moving mice, ΔTRPV4^cMagR expression successfully raises the intracellular calcium level of brain neurons and operates dopamine release from VTA dopaminergic neurons under magnetic stimulation. Remarkably, the effectiveness of ΔTRPV4^cMagR is further validated by magnetic control of mice rotating around the body-axis and freezing-of-gait. This work not only witnesses the magnetoperceptive capacity of MagR, but also provides a promising effective means to manipulate specific neuron populations in brain circuits temporally and remotely.