Broadband ultrasound generator over fiber-optic tip for <i>in vivo</i> emotional stress modulation

Ultrasonic neuromodulation has gained recognition as a promising therapeutic approach. A miniature transducer capable of generating suitable-strength and broadband ultrasound is of great significance for achieving high spatial precision ultrasonic neural stimulation. However, the ultrasound transducer with the above integrated is yet to be challenged. Here, we developed a fiber-optic photoacoustic emitter (FPE) with a diameter of 200 μm, featuring controllable sound intensity and a broadband response (−6 dB bandwidth: 162%). The device integrates MXene (Ti3C2Tx), known for its exceptional photothermal properties, and polydimethylsiloxane, which offers a high thermal expansion coefficient. This FPE, exhibiting high spatial precision (lateral: 163.3 μm, axial: 207 μm), is capable of selectively activating neurons in targeted regions. Using the TetTagging method to selectively express a cfos-promoter-inducible mCHERRY gene within the medial prefrontal cortex (mPFC), we found that photoacoustic stimulation significantly and temporarily activated the neurons. In vivo fiber photometry demonstrated that photoacoustic stimulation induced substantial calcium transients in mPFC neurons. Furthermore, we confirmed that photoacoustic stimulation of the mPFC using FPE markedly alleviates acute social defeat stress-induced emotional stress in mice. This work demonstrates the potential of FPEs for clinical applications, with a particular focus on modulating neural activity to regulate emotions.