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

Publication 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

  • 2,222
    Page views
  • 433
    Downloads
  • 18
    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. Medicine
    2. Neuroscience
    Sachin Sharma, Russell Littman ... Olujimi A Ajijola
    Research Article Updated

    The cell bodies of postganglionic sympathetic neurons innervating the heart primarily reside in the stellate ganglion (SG), alongside neurons innervating other organs and tissues. Whether cardiac-innervating stellate ganglionic neurons (SGNs) exhibit diversity and distinction from those innervating other tissues is not known. To identify and resolve the transcriptomic profiles of SGNs innervating the heart, we leveraged retrograde tracing techniques using adeno-associated virus (AAV) expressing fluorescent proteins (GFP or Td-tomato) with single cell RNA sequencing. We investigated electrophysiologic, morphologic, and physiologic roles for subsets of cardiac-specific neurons and found that three of five adrenergic SGN subtypes innervate the heart. These three subtypes stratify into two subpopulations; high (NA1a) and low (NA1b and NA1c) neuropeptide-Y (NPY) -expressing cells, exhibit distinct morphological, neurochemical, and electrophysiologic characteristics. In physiologic studies in transgenic mouse models modulating NPY signaling, we identified differential control of cardiac responses by these two subpopulations to high and low stress states. These findings provide novel insights into the unique properties of neurons responsible for cardiac sympathetic regulation, with implications for novel strategies to target specific neuronal subtypes for sympathetic blockade in cardiac disease.

    1. Neuroscience
    Hang Hu, Rachel E Hostetler, Ariel Agmon
    Research Article Updated

    Oscillations of extracellular voltage, reflecting synchronous, rhythmic activity in large populations of neurons, are a ubiquitous feature in the mammalian brain, and are thought to subserve important, if not fully understood roles in normal and abnormal brain function. Oscillations at different frequency bands are hallmarks of specific brain and behavioral states. At the higher end of the spectrum, 150-200 Hz ripples occur in the hippocampus during slow-wave sleep, and ultrafast (400-600 Hz) oscillations arise in the somatosensory cortices of humans and several other mammalian species in response to peripheral nerve stimulation or punctate sensory stimuli. Here we report that brief optogenetic activation of thalamocortical axons, in brain slices from mouse somatosensory (barrel) cortex, elicited in the thalamorecipient layer local field potential (LFP) oscillations which we dubbed “ripplets”. Ripplets originated in the postsynaptic cortical network and consisted of a precisely repeating sequence of 2‑5 negative transients, closely resembling hippocampal ripples but, at ~400 Hz, over twice as fast. Fast-spiking (FS) inhibitory interneurons fired highly synchronous 400 Hz spike bursts entrained to the LFP oscillation, while regular-spiking (RS), excitatory neurons typically fired only 1-2 spikes per ripplet, in antiphase to FS spikes, and received synchronous sequences of alternating excitatory and inhibitory inputs. We suggest that ripplets are an intrinsically generated cortical response to a strong, synchronous thalamocortical volley, and could provide increased bandwidth for encoding and transmitting sensory information. Importantly, optogenetically induced ripplets are a uniquely accessible model system for studying synaptic mechanisms of fast and ultrafast cortical and hippocampal oscillations.