Neuromodulation at high spatial resolution poses great significance in advancing fundamental knowledge in the field of neuroscience and offering novel clinical treatments.Here,we developed a tapered fiber optoacoustic...Neuromodulation at high spatial resolution poses great significance in advancing fundamental knowledge in the field of neuroscience and offering novel clinical treatments.Here,we developed a tapered fiber optoacoustic emitter(TFOE)generating an ultrasound field with a high spatial precision of 39.6 pm,enabling optoacoustic activation of single neurons or subcellular structures,such as axons and dendrites.Temporally,a single acoustic pulse of sub-microsecond converted by the TFOE from a single laser pulse of 3 ns is shown as the shortest acoustic stimuli so far for successful neuron activation.The precise ultrasound generated by the TFOE enabled the integration of the optoacoustic stimulation with highly stable patch-clamp recording on single neurons.Direct measurements of the electrical response of single neurons to acoustic stimulation,which is difficult for conventional ultrasound stimulation,have been demonstrated.By coupling TFOE with ex vivo brain slice electrophysiology,we unveil cell-type-specific responses of excitatory and inhibitory neurons to acoustic stimulation.These results demonstrate that TFOE is a non-genetic single-cell and sub-cellular modulation technology,which could shed new insights into the mechanism of ultrasound neurostimulation.展开更多
High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases.Current non-invasive neuromodulation methods offer limited precision at the milimeter level.Here,we report op...High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases.Current non-invasive neuromodulation methods offer limited precision at the milimeter level.Here,we report opticallygenerated focused ultrasound(OFUS)for non-invasive brain stimulation with ultrahigh precision.OFUS is generated by a soft optoacoustic pad(SOAP)fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film.SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83μm,which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound(tFUS).Here,we show effective OFUS neurostimulation in vitro with a single ultrasound cycle.We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo.An acoustic energy of 0.6 mJ/cm?,four orders of magnitude less than that of tFUS,is suffcient for successful OFUS neurostimulation.OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision noninvasively.展开更多
基金Brain Initiative R01 NS109794 to J.-X.C.and C.Y.National Institute of Health,United States,R01 NS052281 to JAW.
文摘Neuromodulation at high spatial resolution poses great significance in advancing fundamental knowledge in the field of neuroscience and offering novel clinical treatments.Here,we developed a tapered fiber optoacoustic emitter(TFOE)generating an ultrasound field with a high spatial precision of 39.6 pm,enabling optoacoustic activation of single neurons or subcellular structures,such as axons and dendrites.Temporally,a single acoustic pulse of sub-microsecond converted by the TFOE from a single laser pulse of 3 ns is shown as the shortest acoustic stimuli so far for successful neuron activation.The precise ultrasound generated by the TFOE enabled the integration of the optoacoustic stimulation with highly stable patch-clamp recording on single neurons.Direct measurements of the electrical response of single neurons to acoustic stimulation,which is difficult for conventional ultrasound stimulation,have been demonstrated.By coupling TFOE with ex vivo brain slice electrophysiology,we unveil cell-type-specific responses of excitatory and inhibitory neurons to acoustic stimulation.These results demonstrate that TFOE is a non-genetic single-cell and sub-cellular modulation technology,which could shed new insights into the mechanism of ultrasound neurostimulation.
基金This work is supported by R01 NS109794 to J.X.C.and C.Y.and R01 HL 125385 to J.-X.CResearch reported in this publication was supported by the Boston University Micro and Nano Imaging Facility and the Office of the Director,National Institutes of Health of the National Institutes of Health under award Number S100D024993.
文摘High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases.Current non-invasive neuromodulation methods offer limited precision at the milimeter level.Here,we report opticallygenerated focused ultrasound(OFUS)for non-invasive brain stimulation with ultrahigh precision.OFUS is generated by a soft optoacoustic pad(SOAP)fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film.SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83μm,which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound(tFUS).Here,we show effective OFUS neurostimulation in vitro with a single ultrasound cycle.We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo.An acoustic energy of 0.6 mJ/cm?,four orders of magnitude less than that of tFUS,is suffcient for successful OFUS neurostimulation.OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision noninvasively.
