Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation

  1. Xiling Li
  2. Pragya Goel
  3. Catherine Chen
  4. Varun Angajala
  5. Xun Chen
  6. Dion K Dickman  Is a corresponding author
  1. University of Southern California, United States

Abstract

Postsynaptic compartments can be specifically modulated during various forms of synaptic plasticity, but it is unclear whether this precision is shared at presynaptic terminals. Presynaptic Homeostatic Plasticity (PHP) stabilizes neurotransmission at the Drosophila neuromuscular junction, where a retrograde enhancement of presynaptic neurotransmitter release compensates for diminished postsynaptic receptor functionality. To test the specificity of PHP induction and expression, we have developed a genetic manipulation to reduce postsynaptic receptor expression at one of the two muscles innervated by a single motor neuron. We find that PHP can be induced and expressed at a subset of synapses, over both acute and chronic time scales, without influencing transmission at adjacent release sites. Further, homeostatic modulations to CaMKII, vesicle pools, and functional release sites are compartmentalized and do not spread to neighboring pre- or post-synaptic structures. Thus, both PHP induction and expression mechanisms are locally transmitted and restricted to specific synaptic compartments.

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. Xiling Li

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Pragya Goel

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Catherine Chen

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Varun Angajala

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Xun Chen

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Dion K Dickman

    Department of Neurobiology, University of Southern California, Los Angeles, United States
    For correspondence
    dickman@usc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1884-284X

Funding

National Institute of Neurological Disorders and Stroke (NS091546)

  • Dion K Dickman

Whitehall Foundation

  • Dion K Dickman

Klingenstein-Simons Foundation

  • Dion K Dickman

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

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Version history

  1. Received: December 14, 2017
  2. Accepted: April 4, 2018
  3. Accepted Manuscript published: April 5, 2018 (version 1)
  4. Version of Record published: April 30, 2018 (version 2)
  5. Version of Record updated: March 6, 2019 (version 3)

Copyright

© 2018, Li 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

  • 3,295
    views
  • 533
    downloads
  • 48
    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. Xiling Li
  2. Pragya Goel
  3. Catherine Chen
  4. Varun Angajala
  5. Xun Chen
  6. Dion K Dickman
(2018)
Synapse-specific and compartmentalized expression of presynaptic homeostatic potentiation
eLife 7:e34338.
https://doi.org/10.7554/eLife.34338

Share this article

https://doi.org/10.7554/eLife.34338

Further reading

    1. Neuroscience
    Paula Banca, Maria Herrojo Ruiz ... Trevor W Robbins
    Research Article

    This study investigates the goal/habit imbalance theory of compulsion in obsessive-compulsive disorder (OCD), which postulates enhanced habit formation, increased automaticity, and impaired goal/habit arbitration. It directly tests these hypotheses using newly developed behavioral tasks. First, OCD patients and healthy participants were trained daily for a month using a smartphone app to perform chunked action sequences. Despite similar procedural learning and attainment of habitual performance (measured by an objective automaticity criterion) by both groups, OCD patients self-reported higher subjective habitual tendencies via a recently developed questionnaire. Subsequently, in a re-evaluation task assessing choices between established automatic and novel goal-directed actions, both groups were sensitive to re-evaluation based on monetary feedback. However, OCD patients, especially those with higher compulsive symptoms and habitual tendencies, showed a clear preference for trained/habitual sequences when choices were based on physical effort, possibly due to their higher attributed intrinsic value. These patients also used the habit-training app more extensively and reported symptom relief post-study. The tendency to attribute higher intrinsic value to familiar actions may be a potential mechanism leading to compulsions and an important addition to the goal/habit imbalance hypothesis in OCD. We also highlight the potential of smartphone app training as a habit reversal therapeutic tool.

    1. Neuroscience
    Taicheng Huang, Jia Liu
    Research Article

    The fact that objects without proper support will fall to the ground is not only a natural phenomenon, but also common sense in mind. Previous studies suggest that humans may infer objects’ stability through a world model that performs mental simulations with a priori knowledge of gravity acting upon the objects. Here we measured participants’ sensitivity to gravity to investigate how the world model works. We found that the world model on gravity was not a faithful replica of the physical laws, but instead encoded gravity’s vertical direction as a Gaussian distribution. The world model with this stochastic feature fit nicely with participants’ subjective sense of objects’ stability and explained the illusion that taller objects are perceived as more likely to fall. Furthermore, a computational model with reinforcement learning revealed that the stochastic characteristic likely originated from experience-dependent comparisons between predictions formed by internal simulations and the realities observed in the external world, which illustrated the ecological advantage of stochastic representation in balancing accuracy and speed for efficient stability inference. The stochastic world model on gravity provides an example of how a priori knowledge of the physical world is implemented in mind that helps humans operate flexibly in open-ended environments.