1. Neuroscience
Download icon

Dissociated sequential activity and stimulus encoding in the dorsomedial striatum during spatial working memory

  1. Hessameddin Akhlaghpour
  2. Joost Wiskerke
  3. Jung Yoon Choi
  4. Joshua P Taliaferro
  5. Jennifer Au
  6. Ilana Witten  Is a corresponding author
  1. Princeton University, United States
Research Article
  • Cited 35
  • Views 3,595
  • Annotations
Cite this article as: eLife 2016;5:e19507 doi: 10.7554/eLife.19507

Abstract

Several lines of evidence suggest that the striatum has an important role in spatial working memory. The neural dynamics in the striatum have been described in tasks with short delay periods (1-4s), but remain largely uncharacterized for tasks with longer delay periods. We collected and analyzed single unit recordings from the dorsomedial striatum of rats performing a spatial working memory task with delays up to 10s. We found that neurons were activated sequentially, with the sequences spanning the entire delay period. Surprisingly, this sequential activity was dissociated from stimulus encoding activity, which was present in the same neurons, but preferentially appeared towards the onset of the delay period. These observations contrast with descriptions of sequential dynamics during similar tasks in other brains areas, and clarify the contribution of the striatum in spatial working memory.

Article and author information

Author details

  1. Hessameddin Akhlaghpour

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Joost Wiskerke

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Jung Yoon Choi

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Joshua P Taliaferro

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6051-8635

  5. Jennifer Au

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Ilana Witten

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    For correspondence
    iwitten@princeton.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0548-2160

Funding

NSF Office of the Director (GRFP)

  • Hessameddin Akhlaghpour

NIH Office of the Director (5R01MH106689-02)

  • Ilana Witten

McKnight Foundation

  • Ilana Witten

Pew Charitable Trusts

  • Ilana Witten

NIH Office of the Director (1 DP2 DA035149-01)

  • Ilana Witten

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (1876-15) of Princeton University. All surgery was performed under anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Naoshige Uchida, Harvard University, United States

Publication history

  1. Received: July 11, 2016
  2. Accepted: September 15, 2016
  3. Accepted Manuscript published: September 16, 2016 (version 1)
  4. Version of Record published: October 6, 2016 (version 2)

Copyright

© 2016, Akhlaghpour 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

  • 3,595
    Page views
  • 811
    Downloads
  • 35
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Research organism

Further reading

    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Molecular basis for functional connectivity between the voltage sensor and the selectivity filter gate in Shaker K+ channels

    Carlos AZ Bassetto et al.
    Research Article Updated

    In Shaker K+ channels, the S4-S5 linker couples the voltage sensor (VSD) and pore domain (PD). Another coupling mechanism is revealed using two W434F-containing channels: L361R:W434F and L366H:W434F. In L361R:W434F, W434F affects the L361R VSD seen as a shallower charge-voltage (Q-V) curve that crosses the conductance-voltage (G-V) curve. In L366H:W434F, L366H relieves the W434F effect converting a non-conductive channel in a conductive one. We report a chain of residues connecting the VSD (S4) to the selectivity filter (SF) in the PD of an adjacent subunit as the molecular basis for voltage sensor selectivity filter gate (VS-SF) coupling. Single alanine substitutions in this region (L409A, S411A, S412A, or F433A) are enough to disrupt the VS-SF coupling, shown by the absence of Q-V and G-V crossing in L361R:W434F mutant and by the lack of ionic conduction in the L366H:W434F mutant. This residue chain defines a new coupling between the VSD and the PD in voltage-gated channels.

    1. Chromosomes and Gene Expression
    2. Neuroscience

    HAT cofactor TRRAP modulates microtubule dynamics via SP1 signaling to prevent neurodegeneration

    Alicia Tapias et al.
    Research Article Updated

    Brain homeostasis is regulated by the viability and functionality of neurons. HAT (histone acetyltransferase) and HDAC (histone deacetylase) inhibitors have been applied to treat neurological deficits in humans; yet, the epigenetic regulation in neurodegeneration remains elusive. Mutations of HAT cofactor TRRAP (ransformation/translation domain-associated protein) cause human neuropathies, including psychosis, intellectual disability, autism, and epilepsy, with unknown mechanism. Here we show that Trrap deletion in Purkinje neurons results in neurodegeneration of old mice. Integrated transcriptomics, epigenomics, and proteomics reveal that TRRAP via SP1 conducts a conserved transcriptomic program. TRRAP is required for SP1 binding at the promoter proximity of target genes, especially microtubule dynamics. The ectopic expression of Stathmin3/4 ameliorates defects of TRRAP-deficient neurons, indicating that the microtubule dynamics is particularly vulnerable to the action of SP1 activity. This study unravels a network linking three well-known, but up-to-date unconnected, signaling pathways, namely TRRAP, HAT, and SP1 with microtubule dynamics, in neuroprotection.

    1. Neuroscience

    Relationship between simultaneously recorded spiking activity and fluorescence signal in GCaMP6 transgenic mice

    Lawrence Huang et al.
    Tools and Resources

    Fluorescent calcium indicators are often used to investigate neural dynamics, but the relationship between fluorescence and action potentials (APs) remains unclear. Most APs can be detected when the soma almost fills the microscope's field of view, but calcium indicators are often used to image populations of neurons, necessitating a large field of view, generating fewer photons per neuron, and compromising AP detection. Here we characterized the AP-fluorescence transfer function in vivo for 48 layer 2/3 pyramidal neurons in primary visual cortex, with simultaneous calcium imaging and cell-attached recordings from transgenic mice expressing GCaMP6s or GCaMP6f. While most APs were detected under optimal conditions, under conditions typical of population imaging studies only a minority of 1AP and 2AP events were detected (often <10% and ~20-30%, respectively), emphasizing the limits of AP detection under more realistic imaging conditions.