← Explore

High‐Precision Photoacoustic Neural Modulation Uses a Non‐Thermal Mechanism

Guo Chen, Feiyuan Yu, Linli Shi, Carolyn Marar, Zhiyi Du, Danchen Jia, Ji‐Xin Cheng, Chen Yang

Advanced Science 2024 · 10.1002/advs.202403205

in vitro cellhealthycellular imaginginvasive electrophysiology

Abstract

Neuromodulation is a powerful tool for fundamental studies in neuroscience and potential treatments of neurological disorders. Both photoacoustic (PA) and photothermal (PT) effects are harnessed for non-genetic high-precision neural stimulation. Using a fiber-based device excitable by a nanosecond pulsed laser and a continuous wave laser for PA and PT stimulation, respectively, PA and PT neuromodulation is systematically investigated at the single neuron level. These results show that to achieve the same level of neuron activation recorded by Ca 2+ imaging, the laser energy needed for PA stimulation is 1/40 of that needed for PT stimulation. The threshold energy for PA stimulation is found to be further reduced in neurons overexpressing mechano-sensitive channels, indicating direct involvement of mechano-sensitive channels in PA stimulation. Electrophysiology study of single neurons upon PA and PT stimulation is performed by patch clamp recordings. Electrophysiological features induced by PA are distinct from those by PT, confirming that PA and PT stimulation operate through different mechanisms. These insights offer a foundation for the rational design of more efficient and safer non-genetic neural modulation approaches.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjectsnot reported cultures
Sessions per subjectnot applicable
Randomisednot applicable
Blindingnot applicable
Sham / controlundescribed
Auditory controlnot reported
Readout timingonline
Anaesthesianot applicable
Readoutscellular imaging, invasive electrophysiology — Ca2+ imaging (OGD-488, GCaMP6f); whole-cell patch clamp; mCherry thermometry
Direction of effectexcitatoryPhotoacoustic pulse trains evoked Ca2+ responses, subthreshold depolarisations and action potentials in cultured cortical neurons, at about 1/40 of the laser energy needed for photothermal stimulation.
Adverse eventsnot applicableTemperature rise on neurons under photoacoustic conditions was negligible by mCherry fluorescence.

Exposures

Exposure 1: Photoacoustic fiber emitter (candle soot/PDMS) driven by ns pulsed laser

Target: cultured neurons — “cultured cortical neurons”
Device: custom-built · Fiber emitter: 200 um optical fiber tip coated with candle soot and PDMS, driven by a 1030 nm 3 ns laser ✓

Pulse timing
Waveformother patterned
Fundamental frequency (kHz)not reported⚑
Pulse duration (ms)not reported⚑
Pulse repetition frequency (Hz)1,700, 4,230swept✓✓✓⚑
Duty cycle (%)not reported
Sonication duration (s)0.0015, 0.003swept✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)8,000✓✓✓⚑
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot applicable
In-situ pressure (kPa)not applicable
In-situ Isppa (W/cm²)not applicable
In-situ Ispta (W/cm²)not applicable
Pressure, domain unspecified (kPa)5,000✓✓✓⚑
Protocol, in the paper’s words

Nanosecond laser pulses (3 ns, 1030 nm) at 4.23 kHz repetition rate for Ca imaging (1.7 kHz in the ion-channel experiments) delivered as 1.5 ms or 3 ms bursts, average laser power 120 mW, fiber tip about 50 um from the neurons. Photothermal comparison used a CW 1064 nm laser for 10 to 100 ms.

Flags from extraction

  • exposures[0].free_field.pressure_kpa — Peak-to-peak pressure 'over 8 MPa' at 45 uJ per pulse measured by hydrophone 50 um from the tip in water; recorded as 8000, lower bound only.
  • exposures[0].unspecified_domain.pressure_kpa — 5 MPa is an estimate from laser pulse energy for the Ca imaging condition; domain not stated.
  • exposures[0].timing.pulse_duration_ms — 3 ns laser pulse converted to ms.
  • exposures[0].timing.pulse_repetition_frequency_hz — 4.23 kHz for Ca imaging and patch clamp; 1.7 kHz in the pharmacology and overexpression experiments.
  • exposures[0].timing.sonication_duration_s — 1.5 ms and 3 ms bursts; recorded in seconds.
  • exposures[0].fundamental_frequency_khz — Optoacoustic broadband emission; no carrier frequency stated in the text (spectrum shown in a figure only).
  • exposures[0].device.family — Stimulus is laser-generated optoacoustic transients from a fiber emitter, not a conventional ultrasound transducer; scope doubtful (condition B).

Notes: Probable out of scope: optoacoustic transients generated by a pulsed laser at a fiber tip, with a CW-laser photothermal comparison.