Abstract

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.
Original languageEnglish
Pages (from-to)540-552
Number of pages13
JournalBrain Stimulation
Volume16
Issue number2
Early online date30 Jan 2023
DOIs
Publication statusPublished - 1 Mar 2023

Bibliographical note

Funding Information:
This work was completed with the support of the GW4 Alliance (GW4), Medical Research Council ( MRC ), and Bristol Research into Alzheimer's and Care for the Elderly ( BRACE ). This work was supported by Medical Research Council ( MR/N0137941/1 ). The authors gratefully acknowledge the Wolfson Bioimaging Facility for their support and assistance in this work.

Funding Information:
This work was completed with the support of the GW4 Alliance (GW4), Medical Research Council (MRC), and Bristol Research into Alzheimer's and Care for the Elderly (BRACE). This work was supported by Medical Research Council (MR/N0137941/1). The authors gratefully acknowledge the Wolfson Bioimaging Facility for their support and assistance in this work.

Publisher Copyright:
© 2023 The Authors

Fingerprint

Dive into the research topics of 'Ultrasound modulates neuronal potassium currents via ionotropic glutamate receptors'. Together they form a unique fingerprint.

Cite this