Brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampus
Background: Brief transcranial focused ultrasound stimulation (tFUS) is used in cognitive mapping, where it is assumed that the intervention itself does not cause lasting modifications to the underlying networks being targeted. However, how so-called ‘offline’ effects impact the dynamic function of...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Brain Stimulation |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X25003079 |
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| author | William W. Watts Benjamin Clennell James K. Jiang Konoha Izaki-Lee Abhishek Binodh Robyn Cuthell Deniz Tonyali Jon Crompton Rosie Taaffe Alanoud Alqahtani Anna Andrieu Igino Rafael Besinga Kate Heesom Tom G.J. Steward Kwangwook Cho Bruce W. Drinkwater Elek Molnár Daniel J. Whitcomb |
| author_facet | William W. Watts Benjamin Clennell James K. Jiang Konoha Izaki-Lee Abhishek Binodh Robyn Cuthell Deniz Tonyali Jon Crompton Rosie Taaffe Alanoud Alqahtani Anna Andrieu Igino Rafael Besinga Kate Heesom Tom G.J. Steward Kwangwook Cho Bruce W. Drinkwater Elek Molnár Daniel J. Whitcomb |
| author_sort | William W. Watts |
| collection | DOAJ |
| description | Background: Brief transcranial focused ultrasound stimulation (tFUS) is used in cognitive mapping, where it is assumed that the intervention itself does not cause lasting modifications to the underlying networks being targeted. However, how so-called ‘offline’ effects impact the dynamic function of neural circuits is largely unknown. Objectives: To determine the persistent effects of ultrasound stimulation on hippocampal circuit function. Methods: Acute rat hippocampal slices in vitro, and rat hippocampi in vivo, were exposed to 40 s, 5 Hz pulsed ultrasound or sham stimulation. The effects of ultrasound on the dynamic synaptic and circuit function of the hippocampus were assessed through quantitative proteomics and extracellular field electrophysiology. Results: We find that ultrasound stimulation induces persistent and differential changes in protein expression and kinase activity in the hippocampus. This occurs concurrently with an enhancement of basal synaptic transmission and modifications to the susceptibility for the hippocampal circuit to undergo synaptic plasticity. These effects occur via a canonical Akt-dependent metaplastic process. Conclusion: The results indicate that tFUS can fundamentally modulate key signalling mechanisms that are responsible for determining the synaptic efficacy in a neural circuit. Importantly, these effects last beyond the duration of the stimulus. These findings provide a mechanistic insight into the sustained impact of tFUS on network function, and emphasise the importance of considering such effects in animal and human studies. |
| format | Article |
| id | doaj-art-9fa3a816b9534a3a988b67f299c32949 |
| institution | Kabale University |
| issn | 1935-861X |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj-art-9fa3a816b9534a3a988b67f299c329492025-08-26T04:14:13ZengElsevierBrain Stimulation1935-861X2025-09-011851587159910.1016/j.brs.2025.08.014Brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampusWilliam W. Watts0Benjamin Clennell1James K. Jiang2Konoha Izaki-Lee3Abhishek Binodh4Robyn Cuthell5Deniz Tonyali6Jon Crompton7Rosie Taaffe8Alanoud Alqahtani9Anna Andrieu10Igino Rafael Besinga11Kate Heesom12Tom G.J. Steward13Kwangwook Cho14Bruce W. Drinkwater15Elek Molnár16Daniel J. Whitcomb17Bristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UKDepartment of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, UK-Dementia Research Institute, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, SE5 9NU, UKFaculty of Engineering, University of Bristol, Bristol, BS8 1TR, UKSchool of Physiology, Pharmacology and Neuroscience, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS8 1TD, UKBristol Medical School, Faculty of Health and Life Sciences, University of Bristol, Bristol, BS1 3NY, UK; Corresponding author.Background: Brief transcranial focused ultrasound stimulation (tFUS) is used in cognitive mapping, where it is assumed that the intervention itself does not cause lasting modifications to the underlying networks being targeted. However, how so-called ‘offline’ effects impact the dynamic function of neural circuits is largely unknown. Objectives: To determine the persistent effects of ultrasound stimulation on hippocampal circuit function. Methods: Acute rat hippocampal slices in vitro, and rat hippocampi in vivo, were exposed to 40 s, 5 Hz pulsed ultrasound or sham stimulation. The effects of ultrasound on the dynamic synaptic and circuit function of the hippocampus were assessed through quantitative proteomics and extracellular field electrophysiology. Results: We find that ultrasound stimulation induces persistent and differential changes in protein expression and kinase activity in the hippocampus. This occurs concurrently with an enhancement of basal synaptic transmission and modifications to the susceptibility for the hippocampal circuit to undergo synaptic plasticity. These effects occur via a canonical Akt-dependent metaplastic process. Conclusion: The results indicate that tFUS can fundamentally modulate key signalling mechanisms that are responsible for determining the synaptic efficacy in a neural circuit. Importantly, these effects last beyond the duration of the stimulus. These findings provide a mechanistic insight into the sustained impact of tFUS on network function, and emphasise the importance of considering such effects in animal and human studies.http://www.sciencedirect.com/science/article/pii/S1935861X25003079 |
| spellingShingle | William W. Watts Benjamin Clennell James K. Jiang Konoha Izaki-Lee Abhishek Binodh Robyn Cuthell Deniz Tonyali Jon Crompton Rosie Taaffe Alanoud Alqahtani Anna Andrieu Igino Rafael Besinga Kate Heesom Tom G.J. Steward Kwangwook Cho Bruce W. Drinkwater Elek Molnár Daniel J. Whitcomb Brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampus Brain Stimulation |
| title | Brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampus |
| title_full | Brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampus |
| title_fullStr | Brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampus |
| title_full_unstemmed | Brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampus |
| title_short | Brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampus |
| title_sort | brief transcranial focused ultrasound stimulation causes lasting modifications to the synaptic circuitry of the hippocampus |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X25003079 |
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