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

  • 1,274
    views
  • 204
    downloads
  • 13
    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. Neuroscience
    Lenia Amaral, Xiaosha Wang ... Ella Striem-Amit
    Research Article

    Research on brain plasticity, particularly in the context of deafness, consistently emphasizes the reorganization of the auditory cortex. But to what extent do all individuals with deafness show the same level of reorganization? To address this question, we examined the individual differences in functional connectivity (FC) from the deprived auditory cortex. Our findings demonstrate remarkable differentiation between individuals deriving from the absence of shared auditory experiences, resulting in heightened FC variability among deaf individuals, compared to more consistent FC in the hearing group. Notably, connectivity to language regions becomes more diverse across individuals with deafness. This does not stem from delayed language acquisition; it is found in deaf native signers, who are exposed to natural language since birth. However, comparing FC diversity between deaf native signers and deaf delayed signers, who were deprived of language in early development, we show that language experience also impacts individual differences, although to a more moderate extent. Overall, our research points out the intricate interplay between brain plasticity and individual differences, shedding light on the diverse ways reorganization manifests among individuals. It joins findings of increased connectivity diversity in blindness and highlights the importance of considering individual differences in personalized rehabilitation for sensory loss.

    1. Computational and Systems Biology
    2. Neuroscience
    Gabriel Loewinger, Erjia Cui ... Francisco Pereira
    Tools and Resources

    Fiber photometry has become a popular technique to measure neural activity in vivo, but common analysis strategies can reduce the detection of effects because they condense within-trial signals into summary measures, and discard trial-level information by averaging across-trials. We propose a novel photometry statistical framework based on functional linear mixed modeling, which enables hypothesis testing of variable effects at every trial time-point, and uses trial-level signals without averaging. This makes it possible to compare the timing and magnitude of signals across conditions while accounting for between-animal differences. Our framework produces a series of plots that illustrate covariate effect estimates and statistical significance at each trial time-point. By exploiting signal autocorrelation, our methodology yields joint 95% confidence intervals that account for inspecting effects across the entire trial and improve the detection of event-related signal changes over common multiple comparisons correction strategies. We reanalyze data from a recent study proposing a theory for the role of mesolimbic dopamine in reward learning, and show the capability of our framework to reveal significant effects obscured by standard analysis approaches. For example, our method identifies two dopamine components with distinct temporal dynamics in response to reward delivery. In simulation experiments, our methodology yields improved statistical power over common analysis approaches. Finally, we provide an open-source package and analysis guide for applying our framework.