Astrocyte-Selective Wireless Deep Brain Stimulation by Magnetite Nanodiscs at Low Alternating Magnetic Field

Astrocytes are essential regulators of synaptic transmission, brain homeostasis and behavior, and direct astrocyte activation has emerged as a promising therapeutic modality for a broad range of CNS disorders. However, selective activation of astrocytes in vivo currently requires viral transgene delivery, tethered fiber implants, or MRI-scale magnetic fields, limiting deployment across laboratories and translational settings. Here we introduce anti-GLAST-conjugated magnetite vortex nanodiscs (GLAST-MND) that, together with a low-amplitude alternating magnetic field, enable wireless, transgene-free, cell-type-specific astrocyte stimulation. The torque generated by MND is sufficient to trigger mechanosensors without the strong spatial gradient required by prior magnetomechanical glial stimulation approaches. GLAST-MND injected into the mouse dentate gyrus co-localized with the astrocyte membrane marker GLAST in vivo. Fiber-photometry in paired astrocyte (gfaABC1D-GCaMP6f) and neuron (Thy1-GCaMP6s) reporter cohorts showed that stimulation at 25 to 28 mT and 10 Hz evoked astrocyte Calcium responses 2- to 3-fold larger than non-magnetic hematite controls, while the neuron cohort showed no material-specific response. A single intracranial injection sustained stable astrocyte responses across at least five weeks and extended to seven weeks in a smaller follow-up cohort. Immunohistochemistry using the contralateral hemisphere as an internal reference confirmed that GLAST-MND stimulation did not induce local c-Fos, consistent with the absence of downstream neuronal excitation. This approach uses a scalable and affordable magnetic system compatible with freely-behaving animals, opening opportunities for astrocyte-focused neuroscience research and for the future development of astrocyte-targeted therapeutics.