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Npas4 recruits CCK basket cell synapses and enhances cannabinoid-sensitive inhibition in the mouse hippocampus

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Cite as: eLife 2018;7:e35927 doi: 10.7554/eLife.35927

Abstract

Experience-dependent expression of immediate-early gene transcription factors (IEG-TFs) can transiently change the transcriptome of active neurons and initiate persistent changes in cellular function. However, the impact of IEG-TFs on circuit connectivity and function is poorly understood. We investigate the specificity with which the IEG-TF NPAS4 governs experience-dependent changes in inhibitory synaptic input onto CA1 pyramidal neurons (PNs). We show that novel sensory experience selectively enhances somatic inhibition mediated by cholecystokinin-expressing basket cells (CCKBCs) in an NPAS4-dependent manner. NPAS4 specifically increases the number of synapses made onto PNs by individual CCKBCs without altering synaptic properties. Additionally, we find that sensory experience-driven NPAS4 expression enhances depolarization-induced suppression of inhibition (DSI), a short-term form of cannabinoid-mediated plasticity expressed at CCKBC synapses. Our results indicate that CCKBC inputs are a major target of the NPAS4-dependent transcriptional program in PNs and that NPAS4 is an important regulator of plasticity mediated by endogenous cannabinoids.

Article and author information

Author details

  1. Andrea L Hartzell

    University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-6202-6148
  2. Kelly M Martyniuk

    University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. G Stefano Brigidi

    University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel Heinz

    University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Nathalie A Djaja

    University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Anja Payne

    University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Brenda L Bloodgood

    University of California, San Diego, La Jolla, United States
    For correspondence
    blbloodgood@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-4797-9119

Funding

Pew Charitable Trusts (28631)

  • Brenda L Bloodgood

Kinship Foundation (14-SSP-184)

  • Brenda L Bloodgood

Whitehall Foundation (2013-12-88)

  • Brenda L Bloodgood

National Science Foundation (2013154395)

  • Andrea L Hartzell

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations and guidance provided by the Research Compliance and Integrity Program and the Institutional Animal Care and Use Committee (IACUC) at UC San Diego. All of the animals were handled according to the approved IACUC protocol, S12254, of UC San Diego. All surgeries and euthanasia were performed under deep isoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Laura Colgin, Reviewing Editor, The University of Texas at Austin, Center for Learning and Memory, United States

Publication history

  1. Received: February 14, 2018
  2. Accepted: July 19, 2018
  3. Accepted Manuscript published: July 27, 2018 (version 1)

Copyright

© 2018, Hartzell 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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