Ultrasound Stimulations Induce Prolonged Depolarization and Fast Action Potentials in Leech Neurons

Francesca Dedola,Annarita Cutrone,Francesco Paolo Ulloa Severino,Alberto Mazzoni,Leonardo Ricotti,Arianna Menciassi,Silvestro Micera,Nicol&Ograve; Meneghetti,Andrea Cafarelli,Th&Eacute;O Lemaire

doi:10.2139/ssrn.3345552

Abstract

Ultrasound stimulation (US) carries the promise of a selective, reversible, and non-invasive modulation of neural activity without the need for genetic manipulation of neural structures. However, the mechanisms of US-induced generation of action potentials (APs) are still unclear. Here we address this issue by analyzing intracellularly recorded responses to controlled delivery of US of leech nociceptive neurons. US induced a depolarization linearly accumulating in time and outlasting the duration of the stimulation. Spiking activity was reliably induced for an optimal US intensity range. Moreover, we found that APs induced by US differ in smaller amplitude and faster repolarization from those induced by electrical (EL) stimulation in the same cell, but keep the same repolarization rate. These results shed light on the mechanism by which spikes are induced by US and pave the way for designing more efficient US patterns.

Highlights

Ultrasound (US) stimulation is an efficient mean to interact non-invasively with the human body
SUBTHRESHOLD RESPONSES TO US STIMULATION We delivered low-intensity, 490 kHz US in blocks of 3 stimuli of 100 ms each, with a duty cycle (DC) of 5, 50 or 100% (continuous stimulation, all reported in Fig. 1(e)) and a root mean square pressure (Prms) of 8, 12, 16 or 20 kPa
The spatial mapping of the pressure within the acoustic field was measured using a hydrophone and the Prms was evaluated in the Petri dish containing the pinned ganglia (Fig. S2 and Fig. S3)

Summary

Introduction

Ultrasound (US) stimulation is an efficient mean to interact non-invasively with the human body. Beyond its conventional use as an imaging modality [1], US is applied for therapeutic interventions such as ablation therapies and blood-brain barrier reversible opening for drug delivery [2]. Such applications rely on the specific nature of acoustic waves that can be accurately steered through biological tissue, offering the ability to concentrate acoustic energy within small volumes (∼mm3) around deep anatomical targets [3]. Low-intensity low-frequency ultrasound (LILFU) can elicit APs in ex-vivo mouse brain and hippocampal slice cultures [4].

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Results

Conclusion