Laser Recording of Subcellular Neuron Activities

Abstract

Advances in imaging and recording of neural activities with a single neuron resolution have played a significant role in understanding neurological diseases in the past decade. Conventional methods relying on patch-clamp and electrodes are regarded as invasive, whereas fluorescence-based imaging tools are useful but still suffer from a low signal-to-noise ratio and low sensitivity. Here we developed a novel optical imaging and recording system by employing laser emissions to record the action potentials in single neurons and neuronal networks caused by subtle transients (Ca2+concentration) in primary neuronsin vitrowith a subcellular and single-spike resolution. By recording the laser emissions from neurons, we discovered that lasing emissions could be biologically modulated by intracellular activities and extracellular stimulation with >100-fold improvement in detection sensitivity over traditional fluorescence-based measurement. Finally, we showed that ultrasound can wirelessly activate neurons adsorbed with piezoelectric BaTiO3nanoparticles, in which the neuron laser emissions were modulated by ultrasound. Our findings show that ultrasound stimulation can significantly increase the lasing intensity and neuron network response. This work not only opens the door to laser emission recording of intracellular dynamics in neuronal networks but may provide an ultra-sensitive detection method for brain-on-chip applications, optogenetics, and neuro-analysis.

Piezoelectric Nanomaterials Activated by Ultrasound: The Pathway from Discovery to Future Clinical Adoption

“…The process also proved to be reversible: neuron response can be fully recovered a few seconds after switching off the stimulus. 68 These works revealed the safe and reversible nature of the “US-activated piezoelectric nanoparticle stimulation” paradigm and highlighted a correlation between the US power intensity and the probability of activating the BTNP-incubated neurons.…”

Piezoelectric Nanomaterials Activated by Ultrasound in Disease Treatment

“…Integrated piezoelectric BaTiO 3 micromotors were capable of in situ electrical stimulation via the application of an external ultrasound field, further inducing differentiation in neural stem-like PC12 cells (Figure 1) [43]. In investigating the activation mechanism, Chen et al, through measuring the number of spines, calcium transients, and recovery time, confirmed that piezoelectric BaTiO3 nanoparticles can wirelessly activate neurons using ultrasound [41]. Building upon this research, they developed BTNPs decorated with a carbon shell and demonstrated its ultrasound-activated functionality in PC-12 neuron-like cells.…”

“…In investigating the activation mechanism, Chen et al, through measuring the number of spines, calcium transients, and recovery time, confirmed that piezoelectric BaTiO 3 nanoparticles can wirelessly activate neurons using ultrasound [ 41 ]. Building upon this research, they developed BTNPs decorated with a carbon shell and demonstrated its ultrasound-activated functionality in PC-12 neuron-like cells.…”