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Ultrasound neuro-modulation chip: activation of sensory neurons in Caenorhabditis elegans by surface acoustic waves

Wei Zhou, Jingjing Wang, Kaiyue Wang, Bin Huang, Lili Niu, Fei Li, Feiyan Cai, Yan Chen, Xin Liu, Xiaoyan Zhang, Hankui Cheng, Lijun Kang, Long Meng, Hairong Zheng

Lab on a Chip 2017, 17, 1725-1731 · 10.1039/c7lc00163k

invertebratehealthybehaviourcellular imaging

Abstract

Ultrasound neuro-modulation has gained increasing attention as a non-invasive method. In this paper, we present an ultrasound neuro-modulation chip, capable of initiating reversal behaviour and activating neurons of C. elegans under the stimulation of a single-shot, short-pulsed ultrasound. About 85.29% ± 6.17% of worms respond to the ultrasound stimulation exhibiting reversal behaviour. Furthermore, the worms can adapt to the ultrasound stimulation with a lower acoustic pulse duration of stimulation. In vivo calcium imaging shows that the activity of ASH, a polymodal sensory neuron in C. elegans, can be directly evoked by the ultrasound stimulation. On the other hand, AFD, a thermal sensitive neuron, cannot be activated by the ultrasound stimulation using the same parameter and the temperature elevation during the stimulation process is relatively small. Consistent with the calcium imaging results, the tax-4 mutants, which are insensitive to temperature increase, do not show a significant difference in avoidance probability compared to the wild type. Therefore, the mechanical effects induced by ultrasound are the main reason for neural and behavioural modulation of C. elegans. With the advantages of confined acoustic energy on the surface, compatible with standard calcium imaging, this neuro-modulation chip could be a powerful tool for revealing the molecular mechanisms of ultrasound neuro-modulation.

Abstract via europepmc.

SpeciesCaenorhabditis elegans
Subjects25, 23, 34, 17, 13, 25swept animals
Sessions per subject1
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingonline
Anaesthesiaawake
Readoutsbehaviour, cellular imagingReversal/avoidance locomotor behavioural assay (recorded by high-speed CCD camera); GCaMP5.0 calcium imaging in ASH (mechanosensory) and AFD (thermosensory) neurons
Direction of effectexcitatorySingle-pulse surface-acoustic-wave ultrasound stimulation triggered reversal/avoidance behaviour in 85.29% +/- 6.17% of worms and evoked Ca2+ transients in ASH sensory neurons; AFD thermosensory neurons were not activated by the same stimulus despite a small temperature rise, indicating a mechanical rather than thermal mechanism.
Adverse eventsnone observedRepeated ultrasound stimulation caused a transient agar surface temperature elevation of less than 0.5 degrees C; stimulated worms had a normal lifespan (~18 days) and reproductive capacity similar to unexposed worms, with no significant change in movement velocity or pattern.

Exposures

Exposure 1: SAW ultrasound stimulation of C. elegans on neuro-modulation chip

Target: c elegans neurons — “whole worm body / ASH and AFD sensory neurons of C. elegans on an agar surface
Device: custom-built

Pulse timing
Waveformcontinuous
Fundamental frequency (kHz)28,110✓✓
Pulse duration (ms)not applicable
Pulse repetition frequency (Hz)not applicable
Duty cycle (%)not applicable
Sonication duration (s)0.0064, 0.00213swept✓✓
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 estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Worms on an agar surface mounted on interdigital transducers (IDTs) were stimulated with a single-shot radio-frequency ultrasound pulse (surface acoustic wave) of 6.40 ms duration and 5 W electric input power to elicit reversal behaviour and neuronal calcium responses; each worm received only a single stimulus for the main behavioural assay to avoid adaptation. In separate adaptation experiments, worms received repeated stimuli (up to 16 applications) at 10 s or 15 s intervals, with pulse duration reduced to as little as 2.13 ms; adaptation (declining response) was greater at the shorter pulse duration.

Consistency checks: f0 out of range.

Flags from extraction

  • n_subjectsThe paper reports several different group sizes for distinct sub-experiments (e.g., n=34 for the main reversal assay, n=25/23/34 for stimulation-position tests, n=17 for ASH calcium imaging, n=13 for AFD imaging, n=25 for tax-4 mutants) but never a single total number of worms used; recorded as not_reported rather than summed or listed inconsistently.
  • exposures[0].timing.sonication_duration_s6.40 ms and 2.13 ms pulse durations are explicitly stated in the main text; additional intermediate durations are shown only in Fig. 2(c) and are not extracted since figures alone do not count.
  • exposures[0].free_field.isppa_w_cm2The paper reports only electric input power to the transducer (~5 W) rather than an acoustic intensity or pressure at the worm; no ISPPA/ISPTA/pressure value could be extracted.
  • anaesthesiaNo anaesthetic protocol is described for C. elegans; 'awake' is inferred from the description of freely moving, behaviourally responsive worms rather than an explicit statement.