Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons

  1. Travis A Hage
  2. Yujie Sun
  3. Zayd M Khaliq  Is a corresponding author
  1. National Institutes of Health, United States

Abstract

Little is known about the density and function of dendritic spines on midbrain dopamine neurons, or the relative contribution of spine and shaft synapses to excitability. Using Ca2+ imaging, glutamate uncaging, fluorescence recovery after photobleaching and transgenic mice expressing labeled PSD-95, we comparatively analyzed electrical and Ca2+ signaling in spines and shaft synapses of dopamine neurons. Dendritic spines were present on dopaminergic neurons at low densities in live and fixed tissue. Uncaging-evoked potential amplitudes correlated inversely with spine length but positively with the presence of PSD-95. Spine Ca2+ signals were less sensitive to hyperpolarization than shaft synapses, suggesting amplification of spine head voltages. Lastly, activating spines during pacemaking, we observed an unexpected enhancement of spine Ca2+ midway throughout the spike cycle, likely involving recruitment of NMDA receptors and voltage-gated conductances. These results demonstrate functionality of spines in dopamine neurons and reveal a novel modulation of spine Ca2+ signaling during pacemaking.

Article and author information

Author details

  1. Travis A Hage

    Cellular Neurophysiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Yujie Sun

    Cellular Neurophysiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Zayd M Khaliq

    Cellular Neurophysiology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States
    For correspondence
    zayd.khaliq@nih.gov
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Gary L Westbrook, Vollum Institute, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the institutional guidelines recommended by the National Institutes of Health. All animals used were handled according to institutional animal care and use committee (IACUC) protocol ASP#1332 of NIH/NINDS.

Version history

  1. Received: December 18, 2015
  2. Accepted: May 9, 2016
  3. Accepted Manuscript published: May 10, 2016 (version 1)
  4. Version of Record published: June 9, 2016 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 2,434
    views
  • 581
    downloads
  • 13
    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. Travis A Hage
  2. Yujie Sun
  3. Zayd M Khaliq
(2016)
Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons
eLife 5:e13905.
https://doi.org/10.7554/eLife.13905

Share this article

https://doi.org/10.7554/eLife.13905

Further reading

    1. Neuroscience
    Geoffroy Delamare, Yosif Zaki ... Claudia Clopath
    Short Report

    Representational drift refers to the dynamic nature of neural representations in the brain despite the behavior being seemingly stable. Although drift has been observed in many different brain regions, the mechanisms underlying it are not known. Since intrinsic neural excitability is suggested to play a key role in regulating memory allocation, fluctuations of excitability could bias the reactivation of previously stored memory ensembles and therefore act as a motor for drift. Here, we propose a rate-based plastic recurrent neural network with slow fluctuations of intrinsic excitability. We first show that subsequent reactivations of a neural ensemble can lead to drift of this ensemble. The model predicts that drift is induced by co-activation of previously active neurons along with neurons with high excitability which leads to remodeling of the recurrent weights. Consistent with previous experimental works, the drifting ensemble is informative about its temporal history. Crucially, we show that the gradual nature of the drift is necessary for decoding temporal information from the activity of the ensemble. Finally, we show that the memory is preserved and can be decoded by an output neuron having plastic synapses with the main region.

    1. Cell Biology
    2. Neuroscience
    Alexandra Stavsky, Leonardo A Parra-Rivas ... Daniel Gitler
    Short Report

    The cytosolic proteins synucleins and synapsins are thought to play cooperative roles in regulating synaptic vesicle (SV) recycling, but mechanistic insight is lacking. Here, we identify the synapsin E-domain as an essential functional binding-partner of α-synuclein (α-syn). Synapsin E-domain allows α-syn functionality, binds to α-syn, and is necessary and sufficient for enabling effects of α-syn at synapses of cultured mouse hippocampal neurons. Together with previous studies implicating the E-domain in clustering SVs, our experiments advocate a cooperative role for these two proteins in maintaining physiologic SV clusters.