Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse

  1. Erica Tagliatti
  2. Manuela Fadda
  3. Antonio Falace
  4. Fabio Benfenati
  5. Anna Fassio  Is a corresponding author
  1. Fondazione Istituto Italiano di Tecnologia, Italy
  2. University of Genova, Italy
  3. Institut national de la santé et de la recherche médicale, Institut de Neurobiologie de la Méditerranée, France

Abstract

Recycling of synaptic vesicles (SVs) is a fundamental step in the process of neurotransmission. Endocytosed SV can travel directly into the recycling pool or recycle through endosomes but little is known about the molecular actors regulating the switch between these SV recycling routes. ADP ribosylation factor 6 (Arf6) is a small GTPase known to participate in constitutive trafficking between plasma membrane and early endosomes. Here we have morphologically and functionally investigated Arf6-silenced hippocampal synapses and found an activity dependent accumulation of synaptic endosome-like organelles and increased release-competent docked SVs. These features were phenocopied by pharmacological blockage of Arf6 activation. The data reveal an unexpected role for this small GTPase in reducing the size of the readily releasable pool of SVs and in channeling retrieved SVs toward direct recycling rather than endosomal sorting. We propose that Arf6 acts at the presynapse to define the fate of an endocytosed SV.

Article and author information

Author details

  1. Erica Tagliatti

    Center of SynapticNeuroscience, Fondazione Istituto Italiano di Tecnologia, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  2. Manuela Fadda

    Department of Experimental Medicine, University of Genova, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  3. Antonio Falace

    Institut national de la santé et de la recherche médicale, Institut de Neurobiologie de la Méditerranée, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Fabio Benfenati

    Center of SynapticNeuroscience, Fondazione Istituto Italiano di Tecnologia, Genova, Italy
    Competing interests
    The authors declare that no competing interests exist.
  5. Anna Fassio

    Center of SynapticNeuroscience, Fondazione Istituto Italiano di Tecnologia, Genova, Italy
    For correspondence
    afassio@unige.it
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experiments were carried out in accordance with the guidelines established by the European Communities Council (Directive 2010/63/EU of March 4th 2014) and were approved by the Italian Ministry of Health.

Copyright

© 2016, Tagliatti 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

  • 2,722
    views
  • 631
    downloads
  • 52
    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. Erica Tagliatti
  2. Manuela Fadda
  3. Antonio Falace
  4. Fabio Benfenati
  5. Anna Fassio
(2016)
Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse
eLife 5:e10116.
https://doi.org/10.7554/eLife.10116

Share this article

https://doi.org/10.7554/eLife.10116

Further reading

    1. Neuroscience
    Franziska Auer, Katherine Nardone ... David Schoppik
    Research Article

    Cerebellar dysfunction leads to postural instability. Recent work in freely moving rodents has transformed investigations of cerebellar contributions to posture. However, the combined complexity of terrestrial locomotion and the rodent cerebellum motivate new approaches to perturb cerebellar function in simpler vertebrates. Here, we adapted a validated chemogenetic tool (TRPV1/capsaicin) to describe the role of Purkinje cells — the output neurons of the cerebellar cortex — as larval zebrafish swam freely in depth. We achieved both bidirectional control (activation and ablation) of Purkinje cells while performing quantitative high-throughput assessment of posture and locomotion. Activation modified postural control in the pitch (nose-up/nose-down) axis. Similarly, ablations disrupted pitch-axis posture and fin-body coordination responsible for climbs. Postural disruption was more widespread in older larvae, offering a window into emergent roles for the developing cerebellum in the control of posture. Finally, we found that activity in Purkinje cells could individually and collectively encode tilt direction, a key feature of postural control neurons. Our findings delineate an expected role for the cerebellum in postural control and vestibular sensation in larval zebrafish, establishing the validity of TRPV1/capsaicin-mediated perturbations in a simple, genetically tractable vertebrate. Moreover, by comparing the contributions of Purkinje cell ablations to posture in time, we uncover signatures of emerging cerebellar control of posture across early development. This work takes a major step towards understanding an ancestral role of the cerebellum in regulating postural maturation.

    1. Neuroscience
    Zhujun Shao, Mengya Zhang, Qing Yu
    Research Article

    When holding visual information temporarily in working memory (WM), the neural representation of the memorandum is distributed across various cortical regions, including visual and frontal cortices. However, the role of stimulus representation in visual and frontal cortices during WM has been controversial. Here, we tested the hypothesis that stimulus representation persists in the frontal cortex to facilitate flexible control demands in WM. During functional MRI, participants flexibly switched between simple WM maintenance of visual stimulus or more complex rule-based categorization of maintained stimulus on a trial-by-trial basis. Our results demonstrated enhanced stimulus representation in the frontal cortex that tracked demands for active WM control and enhanced stimulus representation in the visual cortex that tracked demands for precise WM maintenance. This differential frontal stimulus representation traded off with the newly-generated category representation with varying control demands. Simulation using multi-module recurrent neural networks replicated human neural patterns when stimulus information was preserved for network readout. Altogether, these findings help reconcile the long-standing debate in WM research, and provide empirical and computational evidence that flexible stimulus representation in the frontal cortex during WM serves as a potential neural coding scheme to accommodate the ever-changing environment.