Nongenetic

Neuromodulation is central to both fundamental neuroscience and the development of next-generation brain-computer interfaces (BCIs). However, most cell-type-specific neuromodulation strategies rely on genetic approaches such as optogenetics, which, despite their high spatiotemporal precision, can perturb intrinsic neuronal properties and raise concerns regarding off-target effects and gene-expression efficiency, thereby limiting clinical translation. Moreover, achieving true bimodal neuromodulation remains challenging, as single-gene expression typically enables either inhibition or excitation, restricting applications to one-way perturbations rather than bimodal control of neural activity. Here, we establish a nongenetic bimodal neuromodulation platform by integrating cholesterol-functionalized gold nanorods (GNR-CLS) with a multifunctional fiber-based neural (MFN) probe for localized photothermal stimulation and validate its functionality in the mouse brain. The MFN probe combines microfluidic delivery, near-infrared (NIR) light transmission, and electrophysiological recording within a single flexible fiber, enabling submillimeter colocalization of nanoparticles and optical stimuli with electrophysiological verification of photothermal neuromodulation. Using this platform, we demonstrate