Reciprocally inhibitory circuits operating with distinct mechanisms are differently robust to perturbation and modulation

  1. Ekaterina Morozova
  2. Peter Newstein
  3. Eve Marder  Is a corresponding author
  1. Brandeis University, United States
  2. University of Oregon, United States


Reciprocal inhibition is a building block in many sensory and motor circuits. We studied the features that underly robustness in reciprocally inhibitory two neuron circuits. We used the dynamic clamp to create reciprocally inhibitory circuits from pharmacologically isolated neurons of the crab stomatogastric ganglion by injecting artificial graded synaptic (ISyn) and hyperpolarization-activated inward (IH) currents. There is a continuum of mechanisms in circuits that generate antiphase oscillations, with 'release' and 'escape' mechanisms at the extremes, and mixed mode oscillations in between these extremes. In release, the active neuron primarily controls the off/on transitions. In escape, the inhibited neuron controls the transitions. We characterized the robustness of escape and release circuits to alterations in circuit parameters, temperature, and neuromodulation. We found that escape circuits rely on tight correlations between synaptic and H conductances to generate bursting but are resilient to temperature increase. Release circuits are robust to variations in synaptic and H conductances but fragile to temperature increase. The modulatory current (IMI) restores oscillations in release circuits but has little effect in escape circuits. Perturbations can alter the balance of escape and release mechanisms and can create mixed mode oscillations. We conclude that the same perturbation can have dramatically different effects depending on the circuits' mechanism of operation that may not be observable from basal circuit activity.

Data availability

Data as been deposited at Zenodo and will be publicly available upon publicationDOI: 10.5281/zenodo.5504612

The following data sets were generated

Article and author information

Author details

  1. Ekaterina Morozova

    Volen Center, Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Peter Newstein

    Biology Department, University of Oregon, Eugene, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Eve Marder

    Volen Center, Brandeis University, Waltham, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9632-5448


National Institute of Health (2 R01 MH046742)

  • Eve Marder

Swartz Foundation (Postdoctoral Fellowship for Theoretical Neuroscience)

  • Ekaterina Morozova

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

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Publication history

  1. Preprint posted: September 19, 2021 (view preprint)
  2. Received: September 30, 2021
  3. Accepted: January 26, 2022
  4. Accepted Manuscript published: February 1, 2022 (version 1)
  5. Version of Record published: February 28, 2022 (version 2)


© 2022, Morozova 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.


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  1. Ekaterina Morozova
  2. Peter Newstein
  3. Eve Marder
Reciprocally inhibitory circuits operating with distinct mechanisms are differently robust to perturbation and modulation
eLife 11:e74363.

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