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Transient ultrasound stimulation has lasting effects on neuronal excitability

Clennell, Benjamin, Steward, Tom G.J., Elley, Meg, Shin, Eunju, Weston, Miles, Drinkwater, Bruce W. and Whitcomb, Daniel J. 2021. Transient ultrasound stimulation has lasting effects on neuronal excitability. Brain Stimulation 14 (2) , pp. 217-225. 10.1016/j.brs.2021.01.003

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Abstract

Background Transcranial ultrasound stimulation can acutely modulate brain activity, but the lasting effects on neurons are unknown. Objective To assess the excitability profile of neurons in the hours following transient ultrasound stimulation. Methods Primary rat cortical neurons were stimulated with a 40 s, 200 kHz pulsed ultrasound stimulation or sham-stimulation. Intrinsic firing properties were investigated through whole-cell patch-clamp recording by evoking action potentials in response to somatic current injection. Recordings were taken at set timepoints following ultrasound stimulation: 0–2 h, 6–8 h, 12–14 h and 24–26 h. Transmission electron microscopy was used to assess synaptic ultrastructure at the same timepoints. Results In the 0–2 h window, neurons stimulated with ultrasound displayed an increase in the mean frequency of evoked action potentials of 32% above control cell levels (p = 0.023). After 4–6 h this increase was measured as 44% (p = 0.0043). By 12–14 h this effect was eliminated and remained absent 24–26 h post-stimulation. These changes to action potential firing occurred in conjunction with statistically significant differences between control and ultrasound-stimulated neurons in action potential half-width, depolarisation rate, and repolarisation rate, that were similarly eliminated by 24 h following stimulation. These effects occurred in the absence of alterations to intrinsic membrane properties or synaptic ultrastructure. Conclusion We report that stimulating neurons with 40 s of ultrasound enhances their excitability for up to 8 h in conjunction with modifications to action potential kinetics. This occurs in the absence of major ultrastructural change or modification of intrinsic membrane properties. These results can inform the application of transcranial ultrasound in experimental and therapeutic settings.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Neuroscience and Mental Health Research Institute (NMHRI)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This is an open access article under the Creative Commons Attribution (CC BY 4.0) licence
Publisher: Elsevier
ISSN: 1935-861X
Date of First Compliant Deposit: 9 May 2022
Date of Acceptance: 6 January 2021
Last Modified: 13 May 2022 11:15
URI: https://orca.cardiff.ac.uk/id/eprint/149621

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