Impaired fast-spiking interneuron function in a genetic mouse model of depression

  1. Jonas-Frederic Sauer
  2. Michael Strüber
  3. Marlene Bartos  Is a corresponding author
  1. Albert-Ludwigs-Universität Freiburg, Germany

Abstract

Rhythmic neuronal activity provides a frame for information coding by co-active cell assemblies. Abnormal brain rhythms are considered as potential pathophysiological mechanisms causing mental disease, but the underlying network defects are largely unknown. We find that mice expressing truncated Disrupted-in-Schizophrenia 1 (Disc1), which mirror a high-prevalence genotype for human psychiatric illness, show depression-related behavior. Theta and low-gamma synchrony in the prelimbic cortex (PrlC) is impaired in Disc1 mice and inversely correlated with the extent of behavioural despair. While weak theta activity is driven by the hippocampus, disturbance of low-gamma oscillations is caused by local defects of parvalbumin (PV)-expressing fast-spiking interneurons (FS-INs). The number of FS-INs is reduced, they receive fewer excitatory inputs, and form fewer release sites on targets. Computational analysis indicates that weak excitatory input and inhibitory output of FS-INs may lead to impaired gamma oscillations. Our data link network defects with a gene mutation underlying depression in humans.

Article and author information

Author details

  1. Jonas-Frederic Sauer

    Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  2. Michael Strüber

    Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany
    Competing interests
    No competing interests declared.
  3. Marlene Bartos

    Physiologisches Institut I, Systemic and Cellular Neurophysiology, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany
    For correspondence
    marlene.bartos@physiologie.uni-freiburg.de
    Competing interests
    Marlene Bartos, Reviewing editor, eLife.

Ethics

Animal experimentation: All in vivo and in vitro examinations were performed in agreement with national legislation and institutional regulations (license nr: G-13/25; X-10/18S) approved by the 'Regierungspräsidium' Freiburg.

Copyright

© 2015, Sauer 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

  • 3,691
    views
  • 950
    downloads
  • 92
    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. Jonas-Frederic Sauer
  2. Michael Strüber
  3. Marlene Bartos
(2015)
Impaired fast-spiking interneuron function in a genetic mouse model of depression
eLife 4:e04979.
https://doi.org/10.7554/eLife.04979

Share this article

https://doi.org/10.7554/eLife.04979

Further reading

    1. Neuroscience
    Sudhanvan Iyer, Kathryn Maxson Jones ... Mary A Majumder
    Review Article

    In this paper, we provide an overview and analysis of the BRAIN Initiative data-sharing ecosystem. First, we compare and contrast the characteristics of the seven BRAIN Initiative data archives germane to data sharing and reuse, namely data submission and access procedures and aspects of interoperability. Second, we discuss challenges, benefits, and future opportunities, focusing on issues largely specific to sharing human data and drawing on N = 34 interviews with diverse stakeholders. The BRAIN Initiative-funded archive ecosystem faces interoperability and data stewardship challenges, such as achieving and maintaining interoperability of data and archives and harmonizing research participants’ informed consents for tiers of access for human data across multiple archives. Yet, a benefit of this distributed archive ecosystem is the ability of more specialized archives to adapt to the needs of particular research communities. Finally, the multiple archives offer ample raw material for network evolution in response to the needs of neuroscientists over time. Our first objective in this paper is to provide a guide to the BRAIN Initiative data-sharing ecosystem for readers interested in sharing and reusing neuroscience data. Second, our analysis supports the development of empirically informed policy and practice aimed at making neuroscience data more findable, accessible, interoperable, and reusable.

    1. Neuroscience
    Gordon H Petty, Randy M Bruno
    Research Article

    Each sensory modality has its own primary and secondary thalamic nuclei. While the primary thalamic nuclei are well understood to relay sensory information from the periphery to the cortex, the role of secondary sensory nuclei is elusive. We trained head-fixed mice to attend to one sensory modality while ignoring a second modality, namely to attend to touch and ignore vision, or vice versa. Arrays were used to record simultaneously from the secondary somatosensory thalamus (POm) and secondary visual thalamus (LP). In mice trained to respond to tactile stimuli and ignore visual stimuli, POm was robustly activated by touch and largely unresponsive to visual stimuli. A different pattern was observed when mice were trained to respond to visual stimuli and ignore touch, with POm now more robustly activated during visual trials. This POm activity was not explained by differences in movements (i.e. whisking, licking, pupil dilation) resulting from the two tasks. Post hoc histological reconstruction of array tracks through POm revealed that subregions varied in their degree of plasticity. LP exhibited similar phenomena. We conclude that behavioral training reshapes activity in secondary thalamic nuclei. Secondary nuclei respond to the same behaviorally relevant, reward-predicting stimuli regardless of stimulus modality.