Target-specific control of olfactory bulb periglomerular cells by GABAergic and cholinergic basal forebrain inputs

  1. Didier De Saint Jan  Is a corresponding author
  1. Centre National de la Recherche Scientifique, France

Abstract

The olfactory bulb (OB), the first relay for odor processing in the brain, receives dense GABAergic and cholinergic long-range projections from basal forebrain (BF) nuclei that provide information about the internal state and behavioral context of the animal. However, the targets, impact and dynamic of these afferents are still unclear. I studied how BF synaptic inputs modulate activity in diverse subtypes of periglomerular (PG) interneurons using optogenetic stimulation and loose cell-attached or whole-cell patch-clamp recording in OB slices from adult mice. GABAergic BF inputs potently blocked PG cells firing except in a minority of calretinin-expressing cells in which GABA release elicited spiking. Parallel cholinergic projections excited a previously overlooked PG cell subtype via synaptic activation of M1 muscarinic receptors. Low frequency stimulation of the cholinergic axons drove persistent firing in these PG cells thereby increasing tonic inhibition in principal neurons. Taken together, these findings suggest that modality-specific BF inputs can orchestrate synaptic inhibition in OB glomeruli using multiple, potentially independent, inhibitory or excitatory target-specific pathways.

Data availability

All numerical data used to construct graphs in each figure are available on ZENODO, https://doi.org/10.5281/zenodo.6259698

The following data sets were generated

Article and author information

Author details

  1. Didier De Saint Jan

    Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France
    For correspondence
    desaintjan@inci-cnrs.unistra.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2459-9703

Funding

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 experiments procedures were approved by the French Ministry and by the local ethic committee for animal experimentation (CREMEAS)(authorization number APAFIS#5250-2016042115058488v3 and v7) . Mice were housed in the animal facility with ad libidum access to food and water. Animals were sacrificed by cervical dislocation following the methods approved by the directive 2010/63/EU of the European Parliament and Council. Surgeries were performed under anesthesia and every effort was made to minimize suffering.

Copyright

© 2022, De Saint Jan

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

  • 1,302
    views
  • 216
    downloads
  • 15
    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. Didier De Saint Jan
(2022)
Target-specific control of olfactory bulb periglomerular cells by GABAergic and cholinergic basal forebrain inputs
eLife 11:e71965.
https://doi.org/10.7554/eLife.71965

Share this article

https://doi.org/10.7554/eLife.71965

Further reading

    1. Immunology and Inflammation
    2. Neuroscience
    Jeremy M Shea, Saul A Villeda
    Research Article

    During aging, microglia – the resident macrophages of the brain – exhibit altered phenotypes and contribute to age-related neuroinflammation. While numerous hallmarks of age-related microglia have been elucidated, the progression from homeostasis to dysfunction during the aging process remains unresolved. To bridge this gap in knowledge, we undertook complementary cellular and molecular analyses of microglia in the mouse hippocampus across the adult lifespan and in the experimental aging model of heterochronic parabiosis. Single-cell RNA-Seq and pseudotime analysis revealed age-related transcriptional heterogeneity in hippocampal microglia and identified intermediate states of microglial aging that also emerge following heterochronic parabiosis. We tested the functionality of intermediate stress response states via TGFβ1 and translational states using pharmacological approaches in vitro to reveal their modulation of the progression to an activated state. Furthermore, we utilized single-cell RNA-Seq in conjunction with in vivo adult microglia-specific Tgfb1 conditional genetic knockout mouse models to demonstrate that microglia advancement through intermediate aging states drives transcriptional inflammatory activation and hippocampal-dependent cognitive decline.

    1. Neuroscience
    William Hockeimer, Ruo-Yah Lai ... James J Knierim
    Research Article

    The hippocampus is believed to encode episodic memory by binding information about the content of experience within a spatiotemporal framework encoding the location and temporal context of that experience. Previous work implies a distinction between positional inputs to the hippocampus from upstream brain regions that provide information about an animal’s location and nonpositional inputs which provide information about the content of experience, both sensory and navigational. Here, we leverage the phenomenon of ‘place field repetition’ to better understand the functional dissociation between positional and nonpositional information encoded in CA1. Rats navigated freely on a novel maze consisting of linear segments arranged in a rectilinear, city-block configuration, which combined elements of open-field foraging and linear-track tasks. Unlike typical results in open-field foraging, place fields were directionally tuned on the maze, even though the animal’s behavior was not constrained to extended, one-dimensional (1D) trajectories. Repeating fields from the same cell tended to have the same directional preference when the fields were aligned along a linear corridor of the maze, but they showed uncorrelated directional preferences when they were unaligned across different corridors. Lastly, individual fields displayed complex time dynamics which resulted in the population activity changing gradually over the course of minutes. These temporal dynamics were evident across repeating fields of the same cell. These results demonstrate that the positional inputs that drive a cell to fire in similar locations across the maze can be behaviorally and temporally dissociated from the nonpositional inputs that alter the firing rates of the cell within its place fields, offering a potential mechanism to increase the flexibility of the system to encode episodic variables within a spatiotemporal framework provided by place cells.