1. Neuroscience
Download icon

The subiculum is a patchwork of discrete subregions

  1. Mark S Cembrowski  Is a corresponding author
  2. Lihua Wang
  3. Andrew L Lemire
  4. Monique Copeland
  5. Salvatore F DiLisio
  6. Jody Clements
  7. Nelson Spruston
  1. Janelia Research Campus, Howard Hughes Medical Institute, United States
Tools and Resources
  • Cited 27
  • Views 3,688
  • Annotations
Cite this article as: eLife 2018;7:e37701 doi: 10.7554/eLife.37701

Abstract

In the hippocampus, the classical pyramidal cell type of the subiculum acts as a primary output, conveying hippocampal signals to a diverse suite of downstream regions. Accumulating evidence suggests that the subiculum pyramidal cell population may actually be comprised of discrete subclasses. Here, we investigated the extent and organizational principles governing pyramidal cell heterogeneity throughout the mouse subiculum. Using single-cell RNA-seq, we find that the subiculum pyramidal cell population can be deconstructed into eight separable subclasses. These subclasses were mapped onto abutting spatial domains, ultimately producing a complex laminar and columnar organization with heterogeneity across classical dorsal-ventral, proximal-distal, and superficial-deep axes. We further show that these transcriptomically defined subclasses correspond to differential protein products and can be associated with specific projection targets. This work deconstructs the complex landscape of subiculum pyramidal cells into spatially segregated subclasses that may be observed, controlled, and interpreted in future experiments.

Data availability

Raw and processed scRNA-seq datasets have been deposited in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus under GEO: GSE113069.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Mark S Cembrowski

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    cembrowskim@janelia.hhmi.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8275-7362

  2. Lihua Wang

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Andrew L Lemire

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Monique Copeland

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Salvatore F DiLisio

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Jody Clements

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Nelson Spruston

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3118-1636

Funding

Howard Hughes Medical Institute

  • Mark S Cembrowski
  • Lihua Wang
  • Andrew L Lemire
  • Monique Copeland
  • Salvatore F DiLisio
  • Jody Clements
  • Nelson Spruston

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

Ethics

Animal experimentation: Experimental procedures were approved by the Institutional Animal Care and Use Committee at the Janelia Research Campus.(protocols 14-118 and 17-159).

Reviewing Editor

  1. Laura Colgin, The University of Texas at Austin, Center for Learning and Memory, United States

Publication history

  1. Received: April 19, 2018
  2. Accepted: October 27, 2018
  3. Accepted Manuscript published: October 30, 2018 (version 1)
  4. Version of Record published: November 9, 2018 (version 2)

Copyright

© 2018, Cembrowski 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

  • 3,688
    Page views
  • 716
    Downloads
  • 27
    Citations

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

    Decoding the brain state-dependent relationship between pupil dynamics and resting state fMRI signal fluctuation

    Filip Sobczak et al.
    Research Article Updated

    Pupil dynamics serve as a physiological indicator of cognitive processes and arousal states of the brain across a diverse range of behavioral experiments. Pupil diameter changes reflect brain state fluctuations driven by neuromodulatory systems. Resting-state fMRI (rs-fMRI) has been used to identify global patterns of neuronal correlation with pupil diameter changes; however, the linkage between distinct brain state-dependent activation patterns of neuromodulatory nuclei with pupil dynamics remains to be explored. Here, we identified four clusters of trials with unique activity patterns related to pupil diameter changes in anesthetized rat brains. Going beyond the typical rs-fMRI correlation analysis with pupil dynamics, we decomposed spatiotemporal patterns of rs-fMRI with principal component analysis (PCA) and characterized the cluster-specific pupil–fMRI relationships by optimizing the PCA component weighting via decoding methods. This work shows that pupil dynamics are tightly coupled with different neuromodulatory centers in different trials, presenting a novel PCA-based decoding method to study the brain state-dependent pupil–fMRI relationship.

    1. Neuroscience

    Task-specific roles of local interneurons for inter- and intraglomerular signaling in the insect antennal lobe

    Debora Fusca, Peter Kloppenburg
    Research Article

    Local interneurons (LNs) mediate complex interactions within the antennal lobe, the primary olfactory system of insects, and the functional analog of the vertebrate olfactory bulb. In the cockroach Periplaneta americana, as in other insects, several types of LNs with distinctive physiological and morphological properties can be defined. Here, we combined whole-cell patch-clamp recordings and Ca2+ imaging of individual LNs to analyze the role of spiking and nonspiking LNs in inter- and intraglomerular signaling during olfactory information processing. Spiking GABAergic LNs reacted to odorant stimulation with a uniform rise in [Ca2+]i in the ramifications of all innervated glomeruli. In contrast, in nonspiking LNs, glomerular Ca2+ signals were odorant specific and varied between glomeruli, resulting in distinct, glomerulus-specific tuning curves. The cell type-specific differences in Ca2+ dynamics support the idea that spiking LNs play a primary role in interglomerular signaling, while they assign nonspiking LNs an essential role in intraglomerular signaling.

    1. Neuroscience

    Dendritic osmosensors modulate activity-induced calcium influx in oxytocinergic magnocellular neurons of the mouse PVN

    Wanhui Sheng et al.
    Research Article Updated

    Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not constant, but the mechanisms through which this relationship can be modulated are not completely understood. Here, we use a combination of electrical and optical recording techniques to quantify activity-induced calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes; however, activity-induced dendritic calcium influx can be robustly regulated by both osmosensitive and non-osmosensitive ion channels located along the dendritic membrane. Overall, this study reveals that dendritic conductivity is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release.