Interneuronal mechanisms of hippocampal theta oscillation in a full-scale model of the rodent CA1 circuit

  1. Marianne J Bezaire  Is a corresponding author
  2. Ivan Raikov
  3. Kelly Burk
  4. Dhrumil Vyas
  5. Ivan Soltesz
  1. Boston University, United States
  2. Stanford University, United States
  3. University of California, Irvine, United States

Abstract

The hippocampal theta rhythm plays important roles in information processing; however, the mechanisms of its generation are not well understood. We developed a data-driven, supercomputer-based, full-scale (1:1) model of the rodent CA1 area and studied its interneurons during theta oscillations. Theta rhythm with phase-locked gamma oscillations and phase-preferential discharges of distinct interneuronal types spontaneously emerged from the isolated CA1 circuit without rhythmic inputs. Perturbation experiments identified parvalbumin-expressing interneurons and neurogliaform cells, as well as interneuronal diversity itself, as important factors in theta generation. These simulations reveal new insights into the spatiotemporal organization of the CA1 circuit during theta oscillations.

Data availability

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

Article and author information

Author details

  1. Marianne J Bezaire

    Department of Psychological and Brain Sciences, Boston University, Boston, United States
    For correspondence
    marianne.bezaire@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6040-3520
  2. Ivan Raikov

    Department of Neurosurgery, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8224-8549
  3. Kelly Burk

    Anatomy & Neurobiology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Dhrumil Vyas

    Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Ivan Soltesz

    Department of Neurosurgery, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (NS35915)

  • Ivan Soltesz

National Science Foundation (IOS-1310378)

  • Ivan Soltesz

National Institutes of Health (F32NS090753)

  • Marianne J Bezaire

National Science Foundation (DGE-0808392)

  • Marianne J Bezaire

NSF XSEDE Allocations (TG-IBN140007,TG-IBN130022,TG-IBN100011)

  • Marianne J Bezaire
  • Ivan Raikov
  • Ivan Soltesz

National Institutes of Health (NS090583)

  • Ivan Soltesz

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

Copyright

© 2016, Bezaire 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

  • 6,962
    views
  • 1,481
    downloads
  • 229
    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. Marianne J Bezaire
  2. Ivan Raikov
  3. Kelly Burk
  4. Dhrumil Vyas
  5. Ivan Soltesz
(2016)
Interneuronal mechanisms of hippocampal theta oscillation in a full-scale model of the rodent CA1 circuit
eLife 5:e18566.
https://doi.org/10.7554/eLife.18566

Share this article

https://doi.org/10.7554/eLife.18566

Further reading

    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease
    Saugat Poudel, Jason Hyun ... Bernhard O Palsson
    Research Article

    The Staphylococcus aureus clonal complex 8 (CC8) is made up of several subtypes with varying levels of clinical burden; from community-associated methicillin-resistant S. aureus USA300 strains to hospital-associated (HA-MRSA) USA500 strains and ancestral methicillin-susceptible (MSSA) strains. This phenotypic distribution within a single clonal complex makes CC8 an ideal clade to study the emergence of mutations important for antibiotic resistance and community spread. Gene-level analysis comparing USA300 against MSSA and HA-MRSA strains have revealed key horizontally acquired genes important for its rapid spread in the community. However, efforts to define the contributions of point mutations and indels have been confounded by strong linkage disequilibrium resulting from clonal propagation. To break down this confounding effect, we combined genetic association testing with a model of the transcriptional regulatory network (TRN) to find candidate mutations that may have led to changes in gene regulation. First, we used a De Bruijn graph genome-wide association study to enrich mutations unique to the USA300 lineages within CC8. Next, we reconstructed the TRN by using independent component analysis on 670 RNA-sequencing samples from USA300 and non-USA300 CC8 strains which predicted several genes with strain-specific altered expression patterns. Examination of the regulatory region of one of the genes enriched by both approaches, isdH, revealed a 38-bp deletion containing a Fur-binding site and a conserved single-nucleotide polymorphism which likely led to the altered expression levels in USA300 strains. Taken together, our results demonstrate the utility of reconstructed TRNs to address the limits of genetic approaches when studying emerging pathogenic strains.

    1. Computational and Systems Biology
    Masaaki Uematsu, Jeremy M Baskin
    Tools and Resources

    Plasmid construction is central to life science research, and sequence verification is arguably its costliest step. Long-read sequencing has emerged as a competitor to Sanger sequencing, with the principal benefit that whole plasmids can be sequenced in a single run. Nevertheless, the current cost of nanopore sequencing is still prohibitive for routine sequencing during plasmid construction. We develop a computational approach termed Simple Algorithm for Very Efficient Multiplexing of Oxford Nanopore Experiments for You (SAVEMONEY) that guides researchers to mix multiple plasmids and subsequently computationally de-mixes the resultant sequences. SAVEMONEY defines optimal mixtures in a pre-survey step, and following sequencing, executes a post-analysis workflow involving sequence classification, alignment, and consensus determination. By using Bayesian analysis with prior probability of expected plasmid construction error rate, high-confidence sequences can be obtained for each plasmid in the mixture. Plasmids differing by as little as two bases can be mixed as a single sample for nanopore sequencing, and routine multiplexing of even six plasmids per 180 reads can still maintain high accuracy of consensus sequencing. SAVEMONEY should further democratize whole-plasmid sequencing by nanopore and related technologies, driving down the effective cost of whole-plasmid sequencing to lower than that of a single Sanger sequencing run.