Long-term potentiation is independent of the C-tail of the GluA1 AMPA receptor subunit

  1. Javier Díaz-Alonso  Is a corresponding author
  2. Wade Morishita
  3. Salvatore Incontro
  4. Jeffrey Simms
  5. Julia Holtzman
  6. Michael Gill
  7. Lennart Mucke
  8. Robert C Malenka
  9. Roger A Nicoll  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Stanford University, United States
  3. Gladstone Institute of Neurological Disease, United States
  4. University of California, San Francisco, United States

Abstract

We tested the proposal that the C-terminal domain (CTD) of the AMPAR subunit GluA1 is required for LTP. We found that a knock-in mouse lacking the CTD of GluA1 expresses normal LTP and spatial memory, assayed by the Morris water maze. Our results support a model in which LTP generates synaptic slots, which capture passively diffusing AMPARs.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Javier Díaz-Alonso

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    For correspondence
    Javier.DiazAlonso@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4980-7441
  2. Wade Morishita

    Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Salvatore Incontro

    Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jeffrey Simms

    Gladstone Institute of Neurological Disease, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Julia Holtzman

    Gladstone Institute of Neurological Disease, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael Gill

    Gladstone Institute of Neurological Disease, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Lennart Mucke

    Gladstone Institute of Neurological Disease, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Robert C Malenka

    Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Roger A Nicoll

    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United States
    For correspondence
    roger.nicoll@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6977-4632

Funding

National Institute of Mental Health (K99MH118425)

  • Javier Díaz-Alonso

National Institute of Mental Health (R01MH070957)

  • Roger A Nicoll

National Institute of Mental Health (R01MH117139)

  • Roger A Nicoll

National Institute of Mental Health (P50MH086403)

  • Robert C Malenka

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

Ethics

Animal experimentation: The authors declare that this study has been performed strictly following all relevant laboratory animal use regulations according to approved institutional animal care and use committee (IACUC) protocols of the University of California, San Francisco (AN170318 and AN183289), and Stanford University (10322).

Reviewing Editor

  1. Linda Overstreet-Wadiche, University of Alabama at Birmingham, United States

Version history

  1. Received: April 18, 2020
  2. Accepted: August 21, 2020
  3. Accepted Manuscript published: August 24, 2020 (version 1)
  4. Version of Record published: September 18, 2020 (version 2)

Copyright

© 2020, Díaz-Alonso 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

  • 2,408
    Page views
  • 456
    Downloads
  • 22
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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. Javier Díaz-Alonso
  2. Wade Morishita
  3. Salvatore Incontro
  4. Jeffrey Simms
  5. Julia Holtzman
  6. Michael Gill
  7. Lennart Mucke
  8. Robert C Malenka
  9. Roger A Nicoll
(2020)
Long-term potentiation is independent of the C-tail of the GluA1 AMPA receptor subunit
eLife 9:e58042.
https://doi.org/10.7554/eLife.58042

Further reading

    1. Neuroscience
    Shai Abramson, Benjamin J Kraus ... Genela Morris
    Short Report Updated

    Analysis of neuronal activity in the hippocampus of behaving animals has revealed cells acting as ‘Time Cells’, which exhibit selective spiking patterns at specific time intervals since a triggering event, and ‘Distance Cells’, which encode the traversal of specific distances. Other neurons exhibit a combination of these features, alongside place selectivity. This study aims to investigate how the task performed by animals during recording sessions influences the formation of these representations. We analyzed data from a treadmill running study conducted by Kraus et al., 2013, in which rats were trained to run at different velocities. The rats were recorded in two trial contexts: a ‘fixed time’ condition, where the animal ran on the treadmill for a predetermined duration before proceeding, and a ‘fixed distance’ condition, where the animal ran a specific distance on the treadmill. Our findings indicate that the type of experimental condition significantly influenced the encoding of hippocampal cells. Specifically, distance-encoding cells dominated in fixed-distance experiments, whereas time-encoding cells dominated in fixed-time experiments. These results underscore the flexible coding capabilities of the hippocampus, which are shaped by over-representation of salient variables associated with reward conditions.

    1. Neuroscience
    Nisarg Desai, Praneet Bala ... Benjamin Hayden
    Tools and Resources

    Because of their close relationship with humans, non-human apes (chimpanzees, bonobos, gorillas, orangutans, and gibbons, including siamangs) are of great scientific interest. The goal of understanding their complex behavior would be greatly advanced by the ability to perform video-based pose tracking. Tracking, however, requires high-quality annotated datasets of ape photographs. Here we present OpenApePose, a new public dataset of 71,868 photographs, annotated with 16 body landmarks of six ape species in naturalistic contexts. We show that a standard deep net (HRNet-W48) trained on ape photos can reliably track out-of-sample ape photos better than networks trained on monkeys (specifically, the OpenMonkeyPose dataset) and on humans (COCO) can. This trained network can track apes almost as well as the other networks can track their respective taxa, and models trained without one of the six ape species can track the held-out species better than the monkey and human models can. Ultimately, the results of our analyses highlight the importance of large, specialized databases for animal tracking systems and confirm the utility of our new ape database.