1. Neuroscience
Download icon

Bidirectional synaptic plasticity rapidly modifies hippocampal representations

  1. Aaron D Milstein  Is a corresponding author
  2. Yiding Li
  3. Katie C Bittner
  4. Christine Grienberger
  5. Ivan Soltesz
  6. Jeffrey C Magee
  7. Sandro Romani
  1. Rutgers, The State University of New Jersey, United States
  2. Howard Hughes Medical Institute, Baylor College of Medicine, United States
  3. Howard Hughes Medical Institute, United States
  4. Stanford University, United States
Research Article
  • Cited 3
  • Views 2,057
  • Annotations
Cite this article as: eLife 2021;10:e73046 doi: 10.7554/eLife.73046

Abstract

Learning requires neural adaptations thought to be mediated by activity-dependent synaptic plasticity. A relatively non-standard form of synaptic plasticity driven by dendritic calcium spikes, or plateau potentials, has been reported to underlie place field formation in rodent hippocampal CA1 neurons. Here we found that this behavioral timescale synaptic plasticity (BTSP) can also reshape existing place fields via bidirectional synaptic weight changes that depend on the temporal proximity of plateau potentials to pre-existing place fields. When evoked near an existing place field, plateau potentials induced less synaptic potentiation and more depression, suggesting BTSP might depend inversely on postsynaptic activation. However, manipulations of place cell membrane potential and computational modeling indicated that this anti-correlation actually results from a dependence on current synaptic weight such that weak inputs potentiate and strong inputs depress. A network model implementing this bidirectional synaptic learning rule suggested that BTSP enables population activity, rather than pairwise neuronal correlations, to drive neural adaptations to experience.

Data availability

The complete dataset, Python code for data analysis and model simulation, and additional MATLAB and Igor analysis scripts are available at https://github.com/neurosutras/BTSP.

The following data sets were generated

Article and author information

Author details

  1. Aaron D Milstein

    Department of Neuroscience and Cell Biology, Rutgers, The State University of New Jersey, Piscataway, United States
    For correspondence
    milstein@cabm.rutgers.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7186-5779
  2. Yiding Li

    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Katie C Bittner

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

    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, 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.
  6. Jeffrey C Magee

    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Sandro Romani

    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:" 0000-0002-4727-4207

Funding

National Institutes of Health (U19NS104590)

  • Aaron D Milstein
  • Ivan Soltesz

National Institute of Mental Health (R01MH121979)

  • Aaron D Milstein

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

Ethics

Animal experimentation: All experimental methods were approved by the Janelia or Baylor College of Medicine Institutional Animal Care and Use Committees (Protocol 12-84 & 15-126).

Reviewing Editor

  1. Katalin Toth, University of Ottawa, Canada

Publication history

  1. Preprint posted: February 5, 2020 (view preprint)
  2. Received: August 13, 2021
  3. Accepted: December 8, 2021
  4. Accepted Manuscript published: December 9, 2021 (version 1)
  5. Accepted Manuscript updated: December 10, 2021 (version 2)
  6. Version of Record published: January 20, 2022 (version 3)

Copyright

© 2021, Milstein 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

  • 2,057
    Page views
  • 403
    Downloads
  • 3
    Citations

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

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)

  1. Further reading

Further reading

    1. Chromosomes and Gene Expression
    2. Neuroscience
    Lesly Calderon et al.
    Research Article Updated

    Cohesin and CTCF are major drivers of 3D genome organization, but their role in neurons is still emerging. Here, we show a prominent role for cohesin in the expression of genes that facilitate neuronal maturation and homeostasis. Unexpectedly, we observed two major classes of activity-regulated genes with distinct reliance on cohesin in mouse primary cortical neurons. Immediate early genes (IEGs) remained fully inducible by KCl and BDNF, and short-range enhancer-promoter contacts at the IEGs Fos formed robustly in the absence of cohesin. In contrast, cohesin was required for full expression of a subset of secondary response genes characterized by long-range chromatin contacts. Cohesin-dependence of constitutive neuronal genes with key functions in synaptic transmission and neurotransmitter signaling also scaled with chromatin loop length. Our data demonstrate that key genes required for the maturation and activation of primary cortical neurons depend on cohesin for their full expression, and that the degree to which these genes rely on cohesin scales with the genomic distance traversed by their chromatin contacts.

    1. Neuroscience
    Li Liu et al.
    Research Article Updated

    Central nervous system (CNS) infections are a major cause of human morbidity and mortality worldwide. Even patients that survive, CNS infections can have lasting neurological dysfunction resulting from immune and pathogen induced pathology. Developing approaches to noninvasively track pathology and immunity in the infected CNS is crucial for patient management and development of new therapeutics. Here, we develop novel MRI-based approaches to monitor virus-specific CD8+ T cells and their relationship to cerebrovascular pathology in the living brain. We studied a relevant murine model in which a neurotropic virus (vesicular stomatitis virus) was introduced intranasally and then entered the brain via olfactory sensory neurons – a route exploited by many pathogens in humans. Using T2*-weighted high-resolution MRI, we identified small cerebral microbleeds as an early form of pathology associated with viral entry into the brain. Mechanistically, these microbleeds occurred in the absence of peripheral immune cells and were associated with infection of vascular endothelial cells. We monitored the adaptive response to this infection by developing methods to iron label and track individual virus specific CD8+ T cells by MRI. Transferred antiviral T cells were detected in the brain within a day of infection and were able to reduce cerebral microbleeds. These data demonstrate the utility of MRI in detecting the earliest pathological events in the virally infected CNS as well as the therapeutic potential of antiviral T cells in mitigating this pathology.