Abstract

AMPARs control fast synaptic communication between neurons and their function relies on auxiliary subunits, which importantly modulate channel properties. Although it has been suggested that AMPARs can bind to TARPs with variable stoichiometry, little is known about the effect that this stoichiometry exerts on certain AMPAR properties. Here we have found that AMPARs show a clear stoichiometry-dependent modulation by the prototypical TARP γ2 although the receptor still needs to be fully saturated with γ2 to show some typical TARP-induced characteristics (i.e. an increase in channel conductance). We also uncovered important differences in the stoichiometric modulation between calcium-permeable and calcium-impermeable AMPARs. Moreover, in heteromeric AMPARs, γ2 positioning in the complex is important to exert certain TARP-dependent features. Finally, by comparing data from recombinant receptors with endogenous AMPAR currents from mouse cerebellar granule cells, we have determined a likely presence of two γ2 molecules at somatic receptors in this cell type.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for all Figures.

Article and author information

Author details

  1. Federico Miguez-Cabello

    Biomedicine, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Nuria Sánchez-Fernández

    Biomedicine, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. Natalia Yefimenko

    Biomedicine, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Xavier Gasull

    Biomedicine, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Esther Gratacòs-Batlle

    Biomedicine, University of Barcelona, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8093-3713
  6. David Soto

    Department of Biomedicine, Medical School, University of Barcelona, Barcelona, Spain
    For correspondence
    davidsoto@ub.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7995-3805

Funding

Ministerio de Economía y Competitividad (BFU2017-83317-P)

  • David Soto

Instituto de Salud Carlos III (RD16/0008/0014)

  • Xavier Gasull

Generalitat de Catalunya (2017SGR737)

  • Xavier Gasull

Instituto de Salud Carlos III (FIS-PI17/00296)

  • Xavier Gasull

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

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Ethics

Animal experimentation: The authors state that the animals used in this study were sacrificed following the guidelines of CEEA-UB (Ethical Committee for Animal Research) from University of Barcelona with the license number OB117/16, of which Dr. David Soto is the responsible principal investigator.

Version history

  1. Received: November 25, 2019
  2. Accepted: May 24, 2020
  3. Accepted Manuscript published: May 26, 2020 (version 1)
  4. Accepted Manuscript updated: May 27, 2020 (version 2)
  5. Version of Record published: June 17, 2020 (version 3)
  6. Version of Record updated: July 27, 2020 (version 4)

Copyright

© 2020, Miguez-Cabello 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

  • 1,520
    views
  • 233
    downloads
  • 7
    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. Federico Miguez-Cabello
  2. Nuria Sánchez-Fernández
  3. Natalia Yefimenko
  4. Xavier Gasull
  5. Esther Gratacòs-Batlle
  6. David Soto
(2020)
AMPAR/TARP stoichiometry differentially modulates channel properties
eLife 9:e53946.
https://doi.org/10.7554/eLife.53946

Share this article

https://doi.org/10.7554/eLife.53946

Further reading

    1. Neuroscience
    Songyao Zhang, Tuo Zhang ... Tianming Liu
    Research Article

    Cortical folding is an important feature of primate brains that plays a crucial role in various cognitive and behavioral processes. Extensive research has revealed both similarities and differences in folding morphology and brain function among primates including macaque and human. The folding morphology is the basis of brain function, making cross-species studies on folding morphology important for understanding brain function and species evolution. However, prior studies on cross-species folding morphology mainly focused on partial regions of the cortex instead of the entire brain. Previously, our research defined a whole-brain landmark based on folding morphology: the gyral peak. It was found to exist stably across individuals and ages in both human and macaque brains. Shared and unique gyral peaks in human and macaque are identified in this study, and their similarities and differences in spatial distribution, anatomical morphology, and functional connectivity were also dicussed.

    1. Neuroscience
    Avani Koparkar, Timothy L Warren ... Lena Veit
    Research Article

    Complex skills like speech and dance are composed of ordered sequences of simpler elements, but the neuronal basis for the syntactic ordering of actions is poorly understood. Birdsong is a learned vocal behavior composed of syntactically ordered syllables, controlled in part by the songbird premotor nucleus HVC (proper name). Here, we test whether one of HVC’s recurrent inputs, mMAN (medial magnocellular nucleus of the anterior nidopallium), contributes to sequencing in adult male Bengalese finches (Lonchura striata domestica). Bengalese finch song includes several patterns: (1) chunks, comprising stereotyped syllable sequences; (2) branch points, where a given syllable can be followed probabilistically by multiple syllables; and (3) repeat phrases, where individual syllables are repeated variable numbers of times. We found that following bilateral lesions of mMAN, acoustic structure of syllables remained largely intact, but sequencing became more variable, as evidenced by ‘breaks’ in previously stereotyped chunks, increased uncertainty at branch points, and increased variability in repeat numbers. Our results show that mMAN contributes to the variable sequencing of vocal elements in Bengalese finch song and demonstrate the influence of recurrent projections to HVC. Furthermore, they highlight the utility of species with complex syntax in investigating neuronal control of ordered sequences.