Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons

Abstract

The tonic activity of striatal cholinergic interneurons (CINs) is modified differentially by their afferent inputs. Although their unitary synaptic currents are identical, in most CINs cortical inputs onto distal dendrites only weakly entrain them, whereas proximal thalamic inputs trigger abrupt pauses in discharge in response to salient external stimuli. To test whether the dendritic expression of the active conductances that drive autonomous discharge contribute to the CINs' capacity to dissociate cortical from thalamic inputs, we used an optogenetics-based method to quantify dendritic excitability in mouse CINs. We found that the persistent sodium (NaP) current gave rise to dendritic boosting, and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) current gave rise to a subhertz membrane resonance. This resonance may underlie our novel finding of an association between CIN pauses and internally-generated slow wave events in sleeping non-human primates. Moreover, our method indicated that dendritic NaP and HCN currents were preferentially expressed in proximal dendrites. We validated the non-uniform distribution of NaP currents: pharmacologically; with two-photon imaging of dendritic back-propagating action potentials; and by demonstrating boosting of thalamic, but not cortical, inputs by NaP currents. Thus, the localization of active dendritic conductances in CIN dendrites mirrors the spatial distribution of afferent terminals and may promote their differential responses to thalamic vs. cortical inputs.

Data availability

Tables with all data points used in the figures is available at Open Science Framework: https://osf.io/yxej3/

Article and author information

Author details

  1. Osnat Oz

    Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Lior Matityahu

    Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Aviv Mizrahi-Kliger

    Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Alexander Kaplan

    Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Noa Berkowitz

    Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Lior Tiroshi

    Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Hagai Bergman

    Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2402-6673
  8. Joshua A Goldberg

    Department of Medical Neurobiology, Hebrew University of Jerusalem, Jerusalem, Israel
    For correspondence
    joshua.goldberg2@mail.huji.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5740-4087

Funding

European Research Council (646886)

  • Joshua A Goldberg

Israel Science Foundation (2051/20)

  • Hagai Bergman

Deutsche Forschungsgemeinschaft (CRC TRR295)

  • Hagai Bergman

Israel Science Foundation (154/14)

  • Joshua A Goldberg

Israel Science Foundation (155/14)

  • Joshua A Goldberg

U.S.-Israel Binational Science Foundation (2017020)

  • Joshua A Goldberg

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jun Ding, Stanford University, United States

Ethics

Animal experimentation: All experimental protocols were conducted in accordance with the NationalInstitutes of Health Guide for the Care and Use of Laboratory Animals, and with the Hebrew University guidelines for the use and care of laboratory animals in research. The experiments adhered to, received prior written approval from and were supervised by the Institutional Animal Care and Use Committee of the Faculty of Medicine, under protocols: MD-16-13518-4 (H.B.) and MD-18-15657-3 (J.A.G.).

Version history

  1. Preprint posted: November 30, 2021 (view preprint)
  2. Received: December 2, 2021
  3. Accepted: July 9, 2022
  4. Accepted Manuscript published: July 11, 2022 (version 1)
  5. Accepted Manuscript updated: July 12, 2022 (version 2)
  6. Version of Record published: July 21, 2022 (version 3)

Copyright

© 2022, Oz et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Osnat Oz
  2. Lior Matityahu
  3. Aviv Mizrahi-Kliger
  4. Alexander Kaplan
  5. Noa Berkowitz
  6. Lior Tiroshi
  7. Hagai Bergman
  8. Joshua A Goldberg
(2022)
Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons
eLife 11:e76039.
https://doi.org/10.7554/eLife.76039

Share this article

https://doi.org/10.7554/eLife.76039

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