Microelectrode arrays (MEA) for measuring spatio-temporal neural activity generated by low-energy focused ultrasound (LEFUS) in ex vivo brain slices

Abstract

The objective of this project was to study the electrical activities elicited by Low-Energy Focused Ultrasound (LEFUS) neurostimulation in ex vivo mouse hippocampal brain slices using a MicroElectrode Array (MEA) system. A mixed LEFUS/MEA platform was developed for spatial-temporal recording of neural responses induced by LEFUS exposures in ex-vivo hippocampal brain slices from a mouse model. Hippocampal slices were maintained functional in the 60 electrode MEA chip by perfusion with artificial cerebrospinal fluid. The LEFUS system consisted of a 1.78-MHz focused transducer (diameter: 15 mm, radius of curvature: 15 mm). LEFUS pulses (1.1 MPa, 284–568 cycles) were applied on slices at pulse repetition frequencies in the range of 0.2–1 Hz. Recorded signals resulting from LEFUS stimulation were characterized by negative deflections corresponding to LEFUS artifacts, followed by positive deflections corresponding to electrophysiological responses several milliseconds afterwards. This setup thus allows for the recording and differentiation of fiber volleys (latency ≈ 1–5 ms) and post-synaptic potentials (amplitude ≈ 100–800 μV) as a result of LEFUS stimulation. Such responses were observed in several electrodes across the MEA matrix while exhibiting a progressive drop in amplitude after every applied pulse (Long-term depression). [This project was supported by the French National Research Agency (ANR-16-TERC-0017) the LabEx DevWeCan, and the Focused Ultrasound Foundation (Centers of Excellence).]The objective of this project was to study the electrical activities elicited by Low-Energy Focused Ultrasound (LEFUS) neurostimulation in ex vivo mouse hippocampal brain slices using a MicroElectrode Array (MEA) system. A mixed LEFUS/MEA platform was developed for spatial-temporal recording of neural responses induced by LEFUS exposures in ex-vivo hippocampal brain slices from a mouse model. Hippocampal slices were maintained functional in the 60 electrode MEA chip by perfusion with artificial cerebrospinal fluid. The LEFUS system consisted of a 1.78-MHz focused transducer (diameter: 15 mm, radius of curvature: 15 mm). LEFUS pulses (1.1 MPa, 284–568 cycles) were applied on slices at pulse repetition frequencies in the range of 0.2–1 Hz. Recorded signals resulting from LEFUS stimulation were characterized by negative deflections corresponding to LEFUS artifacts, followed by positive deflections corresponding to electrophysiological responses several milliseconds afterwards. This setup thus allows for the ...