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Integrating ultrasonic neuromodulation with fiber photometry

Aditya Vasan, Uri Magaram, Janki Patel, James Friend, Sreekanth H. Chalasani

Frontiers in Acoustics 2023 · 10.3389/facou.2023.1326759

rodenthealthyother

Abstract

Ultrasound has been used to modulate neural activity in rodents and primates; however, combining ultrasound stimulation with in vivo imaging in freely moving animals has been challenging. Here, we design and validate a transducer to overcome these challenges in the rodent. We develop a head-mounted ultrasound transducer that can be combined with a fiber photometry system. This combination allows us to monitor ultrasound-evoked responses in striatal neurons in awake and freely moving animals. Together, this system allows for a high-resolution analysis of ultrasound-evoked biology at the level of both neural circuits and behavior in freely moving animals, critical to providing a mechanistic understanding of ultrasound neuromodulation.

Abstract via crossref.

Speciesmouse (ChAT-IRES-Cre)
Subjects5 animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlother
Readout timingonline
Anaesthesiaawake
Readoutsother — fiber photometry of GCaMP6s calcium signal in striatal cholinergic neurons
Direction of effectexcitatoryAll five animals showed increased cholinergic GCaMP6s fluorescence in the 3 s after ultrasound compared with sham (control pulses at zero amplifier gain).
Adverse eventsnot reportedTemperature rise in striatum measured ex vivo with a fiber optic hydrophone did not exceed 0.1 C; the mechanical index is stated as 0.19.

Exposures

Exposure 1: head-mounted 6.56 MHz transducer, dorsal striatum

Target: dorsal striatum — “dorsal striatum”
Device: custom-built · custom single-crystal lithium niobate transducer (128YX cut), 5 x 5 mm, 500 um thick

Pulse timing
Waveformnot reported
Fundamental frequency (kHz)6,560✓✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)not reported
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatemeasurementmean or range across subjects
In-situ pressure (kPa)300, 500swept✓✓✓⚑
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Pulse timing, PRF, duty cycle and stimulus duration are not stated. Ultrasound ON trials were interspersed with control pulses run at zero amplifier gain; the response was quantified in the 3-s window after stimulus delivery.

Flags from extraction

  • exposures[0].in_situ.pressure_kpa — 0.3-0.5 MPa peak negative pressure was measured through the intact skull in an ex vivo head preparation (fiber optic hydrophone in striatum) at varying input powers; not clear which level was used in the photometry trials.
  • exposures[0].timing.waveform — Paper gives no pulse timing at all.
  • auditory_control — Paper argues 6.56 MHz is outside the mouse hearing range; no control experiment, so recorded as 'other'.
  • n_subjects — N = 5 for photometry; other numbers (6, 5-6) refer to rotarod and open-field tests without ultrasound output.
  • readouts — Fiber photometry does not fit a listed readout; recorded as other.
  • exposures[0].device.family — Transducer fabricated in-house (authors' own lithium niobate element).