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Acoustically Targeted Chemogenetics for Noninvasive Control of Neural Circuits

Szablowski, Jerzy O. and Lee-Gosselin, Audrey and Lue, Brian and Malounda, Dina and Shapiro, Mikhail G. (2018) Acoustically Targeted Chemogenetics for Noninvasive Control of Neural Circuits. Nature Biomedical Engineering, 2 (7). pp. 475-484. ISSN 2157-846X.

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Neurological and psychiatric disorders are often characterized by dysfunctional neural circuits in specific regions of the brain. Existing treatment strategies, including the use of drugs and implantable brain stimulators, aim to modulate the activity of these circuits. However, they are not cell-type-specific, lack spatial targeting or require invasive procedures. Here, we report a cell-type-specific and non-invasive approach based on acoustically targeted chemogenetics that enables the modulation of neural circuits with spatiotemporal specificity. The approach uses ultrasound waves to transiently open the blood–brain barrier and transduce neurons at specific locations in the brain with virally encoded engineered G-protein-coupled receptors. The engineered neurons subsequently respond to systemically administered designer compounds to activate or inhibit their activity. In a mouse model of memory formation, the approach can modify and subsequently activate or inhibit excitatory neurons within the hippocampus, with selective control over individual brain regions. This technology overcomes some of the key limitations associated with conventional brain therapies.

Item Type:Article
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URLURL TypeDescription ReadCube access Paper ItemAbstract Paper
Szablowski, Jerzy O.0000-0001-7851-5408
Lee-Gosselin, Audrey0000-0002-2431-2741
Malounda, Dina0000-0001-7086-9877
Shapiro, Mikhail G.0000-0002-0291-4215
Additional Information:© 2018 Springer Nature Limited. Received 26 December 2017; Accepted 05 June 2018; Published 09 July 2018. The authors thank M. Zelikowsky for discussions and assistance with the design of the fear conditioning experiments, E. Dumont, R. Jacobs, A. Mukharjee and G. Lu for discussions and R. McCardell for assistance with the initial experiments. We thank the UCLA Translational Pathology Core Laboratory for assistance with the histological samples and Caltech’s Office of Laboratory Animal Research for help with rodent husbandry. This research was supported by the Heritage Medical Research Institute, the Jacobs Institute for Molecular Engineering in Medicine and the Defense Advanced Research Projects Agency (grant W911NF-17-2-0036). Related research in the Shapiro Laboratory is also supported by the Packard Fellowship in Science and Engineering and the Sontag Foundation Distinguished Scientist Award. Author Contributions: J.O.S. and M.G.S. conceived and planned the research. J.O.S. performed the in vivo experiments. J.O.S., B.L., A.L.-G. and D.M. performed the histological experiments. J.O.S. and B.L. analysed the data. J.O.S. and M.G.S. wrote the manuscript with input from all other authors. M.G.S. supervised the research. The authors declare no competing interests. Data availability: The authors declare that all data supporting the findings of this study are available within the paper and its supplementary information. Raw data files are available from the corresponding author upon reasonable request.
Group:Heritage Medical Research Institute, Tianqiao and Chrissy Chen Institute for Neuroscience, Jacobs Institute for Molecular Engineering for Medicine
Funding AgencyGrant Number
Heritage Medical Research InstituteUNSPECIFIED
Joseph J. Jacobs Institute for Molecular Engineering for MedicineUNSPECIFIED
Defense Advanced Research Projects Agency (DARPA)W911NF-17-2-0036
David and Lucile Packard FoundationUNSPECIFIED
Sontag FoundationUNSPECIFIED
Issue or Number:7
Record Number:CaltechAUTHORS:20180108-133221204
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:84169
Deposited By: George Porter
Deposited On:08 Jan 2018 22:10
Last Modified:07 May 2020 19:52

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