Focused ultrasound are considered to be a promising tool for the treatment of neurological conditions, overcoming the limitations of current neurostimulation techniques in terms of spatial resolution and invasiveness. Much evidence to support the feasibility of ultrasound activation of neurons at the systemic level has already been provided, but to this day, the biophysical mechanisms underlying ultrasound neurostimulation are still widely unknown. In order to be able to establish a clear and robust causality between acoustic parameters of the excitation and neurobiological characteristics of the response, it is necessary to work at the cellular level, or alternatively on very simple animal models. The study reported here responds to three objectives. Firstly, to propose a simple nervous model for the study of the ultrasound neurostimulation phenomenon, associated with a clear and simple experimental protocol. Secondly, to compare the characteristics of this model’s nervous response to ultrasound neurostimulation with its nervous response to mechanical and electrical stimulation. Thirdly, to study the role played by certain acoustic parameters in the success rate of the phenomenon of ultrasound stimulation. The feasibility of generating action potentials (APs) in the giant axons of an earthworm’s ventral nerve cord, using pulsed ultrasound stimuli (f = 1.1 MHz, Ncycles = 175–1150, PRF = 25–125 Hz, Npulses = 20, PA = 2.5–7.3 MPa), was demonstrated. The time of generation (TOG) of APs associated with ultrasound stimulation was found to be significantly shorter and more stable than the TOG associated with mechanical stimulation (p < 0.001). By applying a causal approach to interpret the results of this study, it was concluded that, in this model, the nervous response to focused ultrasound is initiated along the afferent neurons, in between the mechanosensors and the synaptic connections with the giant axons. Additionally, early results are provided, highlighting a trend for the success rate of ultrasound neurostimulation and number of APs triggered per response to increase with increasing pulse repetition frequency (p < 0.05 and p < 0.001, respectively), increasing pulse duration and increasing pulse amplitude.
Objective. The brain operates via generation, transmission and integration of neuronal signals and most neurological disorders are related to perturbation of these processes. Neurostimulation by focused ultrasound (FUS) is a promising technology with potential to rival other clinically used techniques for the investigation of brain function and treatment of numerous neurological diseases. The purpose of this study was to characterize spatial and temporal aspects of causal electrophysiological signals directly stimulated by short, single pulses of FUS on ex vivo mouse hippocampal brain slices. Approach. Microelectrode arrays (MEAs) are used to study the spatio-temporal dynamics of extracellular neuronal activities both at the single neuron and neural networks scales. Hence, MEAs provide an excellent platform for characterization of electrical activity generated, modulated and transmitted in response to FUS exposure. In this study, a novel mixed FUS/MEA platform was designed for the spatio-temporal description of the causal responses generated by single 1.78 MHz FUS pulses in ex vivo mouse hippocampal brain slices. Main results. Our results show that FUS pulses can generate local field potentials (LFPs), sustained by synchronized neuronal post-synaptic potentials, and reproducing network activities. LFPs induced by FUS stimulation were found to be repeatable to consecutive FUS pulses though exhibiting a wide range of amplitudes (50–600 μV), durations (20–200 ms), and response delays (10–60 ms). Moreover, LFPs were spread across the hippocampal slice following single FUS pulses thus demonstrating that FUS may be capable of stimulating different neural structures within the hippocampus. Significance. Current knowledge on neurostimulation by ultrasound describes neuronal activity generated by trains of repetitive ultrasound pulses. This novel study details the causal neural responses produced by single-pulse FUS neurostimulation while illustrating the distribution and propagation properties of this neural activity along major neural pathways of the hippocampus.
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