Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition

Abstract

Somatostatin-expressing-interneurons (SOMIs) in the dentate gyrus (DG) control formation of granule cell (GC) assemblies during memory acquisition. Hilar-perforant-path-associated interneurons (HIPP cells) have been considered to be synonymous for DG-SOMIs. Deviating from this assumption, we show two functionally contrasting DG-SOMI-types. The classical feedback-inhibitory HIPPs distribute axon fibers in the molecular layer. They are engaged by converging GC-inputs and provide dendritic inhibition to the DG circuitry. In contrast, SOMIs with axon in the hilus, termed hilar interneurons (HILs), provide perisomatic inhibition onto GABAergic cells in the DG and project to the medial septum. Repetitive activation of glutamatergic inputs onto HIPP cells induces long-lasting-depression (LTD) of synaptic transmission but long-term-potentiation (LTP) of synaptic signals in HIL cells. Thus, LTD in HIPPs may assist flow of spatial information from the entorhinal cortex to the DG, whereas LTP in HILs may facilitate the temporal coordination of GCs with activity patterns governed by the medial septum.

Article and author information

Author details

  1. Mei Yuan

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  2. Thomas Meyer

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  3. Christoph Benkowitz

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  4. Shakuntala Savanthrapadian

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  5. Laura Ansel-Bollepalli

    Institute for Physiology, University of Kiel, Kiel, Germany
    Competing interests
    No competing interests declared.
  6. Angelica Foggetti

    Institute for Physiology, University of Kiel, Kiel, Germany
    Competing interests
    No competing interests declared.
  7. Peer Wulff

    Institute for Physiology, University of Kiel, Kiel, Germany
    Competing interests
    No competing interests declared.
  8. Pepe Alcami

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  9. Claudio Elgueta

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  10. Marlene Bartos

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    For correspondence
    marlene.bartos@physiologie.uni-freiburg.de
    Competing interests
    Marlene Bartos, Reviewing editor, elife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9741-1946

Funding

Deutsche Forschungsgemeinschaft (FOR2143)

  • Marlene Bartos

Volkswagen Foundation (Lichtenberg Award)

  • Marlene Bartos

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

Ethics

Animal experimentation: All animal procedures were performed in accordance to national and european legislations (license no.: G-11/53; X-12/20D).

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Publication history

  1. Received: August 31, 2016
  2. Accepted: April 1, 2017
  3. Accepted Manuscript published: April 3, 2017 (version 1)
  4. Version of Record published: April 18, 2017 (version 2)

Copyright

© 2017, Yuan 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.

Metrics

  • 4,036
    Page views
  • 896
    Downloads
  • 43
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Mei Yuan
  2. Thomas Meyer
  3. Christoph Benkowitz
  4. Shakuntala Savanthrapadian
  5. Laura Ansel-Bollepalli
  6. Angelica Foggetti
  7. Peer Wulff
  8. Pepe Alcami
  9. Claudio Elgueta
  10. Marlene Bartos
(2017)
Somatostatin-positive interneurons in the dentate gyrus of mice provide local- and long-range septal synaptic inhibition
eLife 6:e21105.
https://doi.org/10.7554/eLife.21105

Further reading

    1. Developmental Biology
    2. Neuroscience
    Emily L Heckman, Chris Q Doe
    Research Advance

    The organization of neural circuits determines nervous system function. Variability can arise during neural circuit development (e.g. neurite morphology, axon/dendrite position). To ensure robust nervous system function, mechanisms must exist to accommodate variation in neurite positioning during circuit formation. Previously we developed a model system in the Drosophila ventral nerve cord to conditionally induce positional variability of a proprioceptive sensory axon terminal, and used this model to show that when we altered the presynaptic position of the sensory neuron, its major postsynaptic interneuron partner modified its dendritic arbor to match the presynaptic contact, resulting in functional synaptic input (Sales et al., 2019). Here we investigate the cellular mechanisms by which the interneuron dendrites detect and match variation in presynaptic partner location and input strength. We manipulate the presynaptic sensory neuron by (a) ablation; (b) silencing or activation; or (c) altering its location in the neuropil. From these experiments we conclude that there are two opposing mechanisms used to establish functional connectivity in the face of presynaptic variability: presynaptic contact stimulates dendrite outgrowth locally, whereas presynaptic activity inhibits postsynaptic dendrite outgrowth globally. These mechanisms are only active during an early larval critical period for structural plasticity. Collectively, our data provide new insights into dendrite development, identifying mechanisms that allow dendrites to flexibly respond to developmental variability in presynaptic location and input strength.

    1. Epidemiology and Global Health
    2. Neuroscience
    Lorenza Dall'Aglio, Hannah H Kim ... Henning Tiemeier
    Research Article Updated

    Background:

    Associations between attention-deficit/hyperactivity disorder (ADHD) and brain morphology have been reported, although with several inconsistencies. These may partly stem from confounding bias, which could distort associations and limit generalizability. We examined how associations between brain morphology and ADHD symptoms change with adjustments for potential confounders typically overlooked in the literature (aim 1), and for the intelligence quotient (IQ) and head motion, which are generally corrected for but play ambiguous roles (aim 2).

    Methods:

    Participants were 10-year-old children from the Adolescent Brain Cognitive Development (N = 7722) and Generation R (N = 2531) Studies. Cortical area, volume, and thickness were measured with MRI and ADHD symptoms with the Child Behavior Checklist. Surface-based cross-sectional analyses were run.

    Results:

    ADHD symptoms related to widespread cortical regions when solely adjusting for demographic factors. Additional adjustments for socioeconomic and maternal behavioral confounders (aim 1) generally attenuated associations, as cluster sizes halved and effect sizes substantially reduced. Cluster sizes further changed when including IQ and head motion (aim 2), however, we argue that adjustments might have introduced bias.

    Conclusions:

    Careful confounder selection and control can help identify more robust and specific regions of associations for ADHD symptoms, across two cohorts. We provided guidance to minimizing confounding bias in psychiatric neuroimaging.

    Funding:

    Authors are supported by an NWO-VICI grant (NWO-ZonMW: 016.VICI.170.200 to HT) for HT, LDA, SL, and the Sophia Foundation S18-20, and Erasmus University and Erasmus MC Fellowship for RLM.