Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses

  1. Patricia M Horvath
  2. Michelle K Piazza
  3. Lisa M Monteggia  Is a corresponding author
  4. Ege T Kavalali  Is a corresponding author
  1. Vanderbilt University, United States

Abstract

Synaptic transmission is initiated via spontaneous or action-potential evoked fusion of synaptic vesicles. At excitatory synapses, glutamatergic receptors activated by spontaneous and evoked neurotransmission are segregated. Although inhibitory synapses also transmit signals spontaneously or in response to action potentials, they differ from excitatory synapses in both structure and function. Therefore, we hypothesized that inhibitory synapses may have different organizing principles. We report picrotoxin, a GABAAR antagonist, blocks neurotransmission in a use-dependent manner at rat hippocampal synapses and therefore can be used to interrogate synaptic properties. Using this tool, we uncovered partial segregation of inhibitory spontaneous and evoked neurotransmission. We found up to 40% of the evoked response is mediated through GABAARs which are only activated by evoked neurotransmission. These data indicate GABAergic spontaneous and evoked neurotransmission processes are partially non-overlapping, suggesting they may serve divergent roles in neuronal signaling.

Data availability

All source data files are included in the manuscript and supporting files.

Article and author information

Author details

  1. Patricia M Horvath

    Department of Pharmacology, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  2. Michelle K Piazza

    Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States
    Competing interests
    No competing interests declared.
  3. Lisa M Monteggia

    Department of Neuroscience, Vanderbilt University, Nashville, United States
    For correspondence
    lisa.monteggia@vanderbilt.edu
    Competing interests
    Lisa M Monteggia, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0018-501X
  4. Ege T Kavalali

    Department of Pharmacology, Vanderbilt University, Nashville, United States
    For correspondence
    ege.kavalali@vanderbilt.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1777-227X

Funding

National Institute of General Medical Sciences (T32 GM008203)

  • Patricia M Horvath

National Institute of Mental Health (R01 MH070727)

  • Lisa M Monteggia

National Institute of Mental Health (R01 MH66198)

  • Ege T Kavalali

National Institute of Mental Health (T32MH064913)

  • Michelle K Piazza

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

Ethics

Animal experimentation: Animal procedures conformed to the Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee at UT Southwestern Medical Center ( Animal Protocol Number APN 2016-101416) and at Vanderbilt University School of Medicine (Animal Protocol Number M1800103)

Copyright

© 2020, Horvath 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

  • 5,646
    views
  • 595
    downloads
  • 26
    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. Patricia M Horvath
  2. Michelle K Piazza
  3. Lisa M Monteggia
  4. Ege T Kavalali
(2020)
Spontaneous and evoked neurotransmission are partially segregated at inhibitory synapses
eLife 9:e52852.
https://doi.org/10.7554/eLife.52852

Share this article

https://doi.org/10.7554/eLife.52852

Further reading

    1. Neuroscience
    Vincent Huson, Wade G Regehr
    Research Article

    Unipolar brush cells (UBCs) are excitatory interneurons in the cerebellar cortex that receive mossy fiber (MF) inputs and excite granule cells. The UBC population responds to brief burst activation of MFs with a continuum of temporal transformations, but it is not known how UBCs transform the diverse range of MF input patterns that occur in vivo. Here, we use cell-attached recordings from UBCs in acute cerebellar slices to examine responses to MF firing patterns that are based on in vivo recordings. We find that MFs evoke a continuum of responses in the UBC population, mediated by three different types of glutamate receptors that each convey a specialized component. AMPARs transmit timing information for single stimuli at up to 5 spikes/s, and for very brief bursts. A combination of mGluR2/3s (inhibitory) and mGluR1s (excitatory) mediates a continuum of delayed, and broadened responses to longer bursts, and to sustained high frequency activation. Variability in the mGluR2/3 component controls the time course of the onset of firing, and variability in the mGluR1 component controls the duration of prolonged firing. We conclude that the combination of glutamate receptor types allows each UBC to simultaneously convey different aspects of MF firing. These findings establish that UBCs are highly flexible circuit elements that provide diverse temporal transformations that are well suited to contribute to specialized processing in different regions of the cerebellar cortex.

    1. Neuroscience
    Eleni Hackwell, Sharon R Ladyman ... David R Grattan
    Research Article

    The specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation. GCaMP fibre photometry of arcuate kisspeptin neurons revealed that the normal episodic activity of these neurons is rapidly suppressed in pregnancy and this was maintained throughout early lactation. Deletion of Prlr from arcuate kisspeptin neurons resulted in early reactivation of episodic activity of kisspeptin neurons prior to a premature return of reproductive cycles in early lactation. These observations show dynamic variation in arcuate kisspeptin neuronal activity associated with the hormonal changes of pregnancy and lactation, and provide direct evidence that prolactin action on arcuate kisspeptin neurons is necessary for suppressing fertility during lactation in mice.