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).

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

  • 5,071
    views
  • 1,011
    downloads
  • 77
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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

Share this article

https://doi.org/10.7554/eLife.21105

Further reading

    1. Neuroscience
    Brian C Ruyle, Sarah Masud ... Jose A Morón
    Research Article

    Millions of Americans suffering from Opioid Use Disorders face a high risk of fatal overdose due to opioid-induced respiratory depression (OIRD). Fentanyl, a powerful synthetic opioid, is a major contributor to the rising rates of overdose deaths. Reversing fentanyl overdoses has proved challenging due to its high potency and the rapid onset of OIRD. We assessed the contributions of central and peripheral mu opioid receptors (MORs) in mediating fentanyl-induced physiological responses. The peripherally restricted MOR antagonist naloxone methiodide (NLXM) both prevented and reversed OIRD to a degree comparable to that of naloxone (NLX), indicating substantial involvement of peripheral MORs to OIRD. Interestingly, NLXM-mediated OIRD reversal did not produce aversive behaviors observed after NLX. We show that neurons in the nucleus of the solitary tract (nTS), the first central synapse of peripheral afferents, exhibit a biphasic activity profile following fentanyl exposure. NLXM pretreatment attenuates this activity, suggesting that these responses are mediated by peripheral MORs. Together, these findings establish a critical role for peripheral MORs, including ascending inputs to the nTS, as sites of dysfunction during OIRD. Furthermore, selective peripheral MOR antagonism could be a promising therapeutic strategy for managing OIRD by sparing CNS-driven acute opioid-associated withdrawal and aversion observed after NLX.

    1. Neuroscience
    David C Williams, Amanda Chu ... Michael A McDannald
    Research Advance Updated

    Recognizing and responding to threat cues is essential to survival. Freezing is a predominant threat behavior in rats. We have recently shown that a threat cue can organize diverse behaviors beyond freezing, including locomotion (Chu et al., 2024). However, that experimental design was complex, required many sessions, and had rats receive many foot shock presentations. Moreover, the findings were descriptive. Here, we gave female and male Long Evans rats cue light illumination paired or unpaired with foot shock (eight total) in a conditioned suppression setting using a range of shock intensities (0.15, 0.25, 0.35, or 0.50 mA). We found that conditioned suppression was only observed at higher foot shock intensities (0.35 mA and 0.50 mA). We constructed comprehensive temporal ethograms by scoring 22,272 frames across 12 behavior categories in 200-ms intervals around cue light illumination. The 0.50 mA and 0.35 mA shock-paired visual cues suppressed reward seeking, rearing, and scaling, as well as light-directed rearing and light-directed scaling. These shock-paired visual cues further elicited locomotion and freezing. Linear discriminant analyses showed that ethogram data could accurately classify rats into paired and unpaired groups. Using complete ethogram data produced superior classification compared to behavior subsets, including an immobility subset featuring freezing. The results demonstrate diverse threat behaviors – in a short and simple procedure – containing sufficient information to distinguish the visual fear conditioning status of individual rats.