Ultrasound modulates neuronal potassium currents via ionotropic glutamate receptors.

Autor: Clennell B; Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, BS1 3NY, UK., Steward TGJ; Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, BS1 3NY, UK., Hanman K; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK., Needham T; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK., Benachour J; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK., Jepson M; Wolfson Bioimaging Facility, Faculty of Life Sciences, University of Bristol, Bristol, BS8 1TD, UK., Elley M; Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, BS1 3NY, UK., Halford N; Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, BS1 3NY, UK., Heesom K; Proteomics Facility Faculty of Life Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK., Shin E; School of Life Sciences, Keele University, ST5 5BG, UK., Molnár E; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK., Drinkwater BW; Faculty of Engineering, University of Bristol, Bristol, BS8 1TR, UK., Whitcomb DJ; Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, BS1 3NY, UK. Electronic address: D.J.Whitcomb@Bristol.ac.uk.
Jazyk: angličtina
Zdroj: Brain stimulation [Brain Stimul] 2023 Mar-Apr; Vol. 16 (2), pp. 540-552. Date of Electronic Publication: 2023 Jan 31.
DOI: 10.1016/j.brs.2023.01.1674
Abstrakt: Background: Focused ultrasound stimulation (FUS) has the potential to provide non-invasive neuromodulation of deep brain regions with unparalleled spatial precision. However, the cellular and molecular consequences of ultrasound stimulation on neurons remains poorly understood. We previously reported that ultrasound stimulation induces increases in neuronal excitability that persist for hours following stimulation in vitro. In the present study we sought to further elucidate the molecular mechanisms by which ultrasound regulates neuronal excitability and synaptic function.
Objectives: To determine the effect of ultrasound stimulation on voltage-gated ion channel function and synaptic plasticity.
Methods: Primary rat cortical neurons were exposed to a 40 s, 200 kHz pulsed ultrasound stimulus or sham-stimulus. Whole-cell patch clamp electrophysiology, quantitative proteomics and high-resolution confocal microscopy were employed to determine the effects of ultrasound stimulation on molecular regulators of neuronal excitability and synaptic function.
Results: We find that ultrasound exposure elicits sustained but reversible increases in whole-cell potassium currents. In addition, we find that ultrasound exposure activates synaptic signalling cascades that result in marked increases in excitatory synaptic transmission. Finally, we demonstrate the requirement of ionotropic glutamate receptor (AMPAR/NMDAR) activation for ultrasound-induced modulation of neuronal potassium currents.
Conclusion: These results suggest specific patterns of pulsed ultrasound can induce contemporaneous enhancement of both neuronal excitability and synaptic function, with implications for the application of FUS in experimental and therapeutic settings. Further study is now required to deduce the precise molecular mechanisms through which these changes occur.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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