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Polysynaptic inhibition between striatal cholinergic interneurons shapes their network activity patterns in a dopamine-dependent manner

Dorst, Matthijs C. and Tokarska, Anna and Zhou, Ming and Lee, Kwang and Stagkourakis, Stefanos and Broberger, Christian and Masmanidis, Sotiris and Silberberg, Gilad (2020) Polysynaptic inhibition between striatal cholinergic interneurons shapes their network activity patterns in a dopamine-dependent manner. Nature Communications, 11 . Art. No. 5113. ISSN 2041-1723. https://resolver.caltech.edu/CaltechAUTHORS:20201012-163631929

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Abstract

Striatal activity is dynamically modulated by acetylcholine and dopamine, both of which are essential for basal ganglia function. Synchronized pauses in the activity of striatal cholinergic interneurons (ChINs) are correlated with elevated activity of midbrain dopaminergic neurons, whereas synchronous firing of ChINs induces local release of dopamine. The mechanisms underlying ChIN synchronization and its interplay with dopamine release are not fully understood. Here we show that polysynaptic inhibition between ChINs is a robust network motif and instrumental in shaping the network activity of ChINs. Action potentials in ChINs evoke large inhibitory responses in multiple neighboring ChINs, strong enough to suppress their tonic activity. Using a combination of optogenetics and chemogenetics we show the involvement of striatal tyrosine hydroxylase-expressing interneurons in mediating this inhibition. Inhibition between ChINs is attenuated by dopaminergic midbrain afferents acting presynaptically on D2 receptors. Our results present a novel form of interaction between striatal dopamine and acetylcholine dynamics.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41467-020-18882-yDOIArticle
ORCID:
AuthorORCID
Dorst, Matthijs C.0000-0002-1162-1481
Tokarska, Anna0000-0001-9734-2354
Lee, Kwang0000-0002-2689-0350
Stagkourakis, Stefanos0000-0003-1218-791X
Broberger, Christian0000-0002-7050-8809
Masmanidis, Sotiris0000-0002-8699-3335
Silberberg, Gilad0000-0001-9964-505X
Additional Information:© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received 22 January 2020. Accepted 14 September 2020. Published 09 October 2020. We would like to thank Gilberto Fisone, Giada Spigolon, and Maya Ketzef for the 6-OHDA injections, Elin Dahlberg for technical support, Abdel El Manira, Sten Grillner, and the Silberberg lab, for comments on the paper. This work was supported by the Knut & Alice Wallenberg Foundation (KAW 2014.0051), The European Research Council (ERC 282012), The Swedish Brain Foundation (Hjärnfonden FO2018-0107), The Swedish Medical Research Council (VR-M 2015-02403), Karolinska Institutet Strategic Program for Neuroscience (StratNeuro), and grants from Karolinska Institutet. S.M. was supported by NIH grants NS100050, DA042739, DA005010, and NSF grant DBI-1707408. Open Access funding provided by Karolinska Institutet. Data availability. The data that support the findings of this study are available from the authors on reasonable request, see author contributions for specific data sets. Source data are provided with this paper. Author Contributions. M.C.D. performed and analyzed ex vivo experiments, A.T. and M.Z. designed and performed ex vivo recordings, K.L. performed in vivo recordings, S.S. performed voltammetry experiments, C.B. supervised voltammetry experiments, S.M. designed, supervised, and analyzed in vivo experiments, G.S. designed and supervised the study. All authors contributed to writing the paper. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
Knut and Alice Wallenberg FoundationKAW 2014.0051
European Research Council (ERC)282012
Swedish Brain FoundationFO2018-0107
Swedish Medical Research CouncilVR-M 2015-02403
Karolinska InstitutetUNSPECIFIED
NIHNS100050
NIHDA042739
NIHDA005010
NSFDBI-1707408
Record Number:CaltechAUTHORS:20201012-163631929
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201012-163631929
Official Citation:Dorst, M.C., Tokarska, A., Zhou, M. et al. Polysynaptic inhibition between striatal cholinergic interneurons shapes their network activity patterns in a dopamine-dependent manner. Nat Commun 11, 5113 (2020). https://doi.org/10.1038/s41467-020-18882-y
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106004
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:13 Oct 2020 16:36
Last Modified:13 Oct 2020 16:36

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