Endocannabinoid dynamics gate spike-timing dependent depression and potentiation

  1. Yihui Cui
  2. Ilya Prokin
  3. Hao Xu
  4. Bruno Delord
  5. Stephane Genet
  6. Laurent Venance
  7. Hugues Berry  Is a corresponding author
  1. College de France, France
  2. French Institute for Research in Computer Science and Automation, France
  3. University Pierre et Marie Curie, France

Abstract

Synaptic plasticity is a cardinal cellular mechanism for learning and memory. The endocannabinoid (eCB) system has emerged as a pivotal pathway for synaptic plasticity because of its widely characterized ability to depress synaptic transmission on short- and long-term scales. Recent reports indicate that eCBs also mediate potentiation of the synapse. However it is not known how eCB signaling may support bidirectionality. Here, we combined electrophysiology experiments with mathematical modeling to question the mechanisms of eCB bidirectionality in spike-timing dependent plasticity (STDP) at corticostriatal synapses. We demonstrate that STDP outcome is controlled by eCB levels and dynamics: prolonged and moderate levels of eCB lead to eCB-mediated long-term depression (eCB-tLTD) while short and large eCB transients produce eCB-mediated long-term potentiation (eCB-tLTP). Moreover, we show that eCB-tLTD requires active calcineurin whereas eCB-tLTP necessitates the activity of presynaptic PKA. Therefore, just like glutamate or GABA, eCB form a bidirectional system to encode learning and memory.

Article and author information

Author details

  1. Yihui Cui

    Center for Interdisciplinary Research in Biology, College de France, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Ilya Prokin

    French Institute for Research in Computer Science and Automation, Villeurbanne, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Hao Xu

    Center for Interdisciplinary Research in Biology, College de France, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Bruno Delord

    University Pierre et Marie Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Stephane Genet

    University Pierre et Marie Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Laurent Venance

    Center for Interdisciplinary Research in Biology, College de France, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Hugues Berry

    French Institute for Research in Computer Science and Automation, Villeurbanne, France
    For correspondence
    hugues.berry@inria.fr
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experiments were performed in accordance with local animal welfare committee (Center for Interdisciplinary Research in Biology and EU guidelines, directive 2010/63/EU).

Copyright

© 2016, Cui 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

  • 2,366
    views
  • 615
    downloads
  • 58
    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. Yihui Cui
  2. Ilya Prokin
  3. Hao Xu
  4. Bruno Delord
  5. Stephane Genet
  6. Laurent Venance
  7. Hugues Berry
(2016)
Endocannabinoid dynamics gate spike-timing dependent depression and potentiation
eLife 5:e13185.
https://doi.org/10.7554/eLife.13185

Share this article

https://doi.org/10.7554/eLife.13185

Further reading

    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.

    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.