Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles

  1. Gábor Molnár
  2. Márton Rózsa
  3. Judith Baka
  4. Noémi Holderith
  5. Pál Barzó
  6. Zoltan Nusser
  7. Gábor Tamás  Is a corresponding author
  1. University of Szeged, Hungary
  2. Hungarian Academy of Sciences, Hungary

Abstract

Classic theories link cognitive abilities to synaptic properties and human-specific biophysical features of synapses might contribute to the unparalleled performance of the human cerebral cortex. Paired recordings and multiple probability fluctuation analysis revealed similar quantal sizes, but 4-times more functional release sites in human pyramidal cell to fast-spiking interneuron connections compared to rats. These connections were mediated on average by three synaptic contacts in both species. Each presynaptic active zone (AZ) contains 6.2 release sites in human, but only 1.6 in rats. Electron microscopy (EM) and EM tomography showed that an AZ harbors 4 docked vesicles in human, but only a single one in rats. Consequently, a Katz's functional release site occupies ~0.012 μm2 in the human presynaptic AZ and ~0.025 μm2 in the rat. Our results reveal a robust difference in the biophysical properties of a well-defined synaptic connection of the cortical microcircuit of human and rodents.

Article and author information

Author details

  1. Gábor Molnár

    MTA-SZTE Research Group for Cortical Microcircuits, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  2. Márton Rózsa

    MTA-SZTE Research Group for Cortical Microcircuits, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  3. Judith Baka

    MTA-SZTE Research Group for Cortical Microcircuits, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  4. Noémi Holderith

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0024-3980
  5. Pál Barzó

    Department of Neurosurgery, University of Szeged, Szeged, Hungary
    Competing interests
    The authors declare that no competing interests exist.
  6. Zoltan Nusser

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7004-4111
  7. Gábor Tamás

    MTA-SZTE Research Group for Cortical Microcircuits, University of Szeged, Szeged, Hungary
    For correspondence
    gtamas@bio.u-szeged.hu
    Competing interests
    The authors declare that no competing interests exist.

Funding

European Research Council (INTERIMPACT)

  • Gábor Tamás

European Research Council (293681)

  • Zoltan Nusser

Magyar Tudományos Akadémia (MTA-SZTE Agykergi Neuronhalozatok Kutatocsoport)

  • Gábor Tamás

Magyar Tudományos Akadémia (Lendület, LP2012-29)

  • Zoltan Nusser

Magyar Tudományos Akadémia (Janos Bolyai Scholarship)

  • Noémi Holderith

Nemzeti Kutatási és Technológiai Hivatal (VKSZ_14-1-2015-0155)

  • Gábor Tamás

Nemzeti Agykutatasi Program (NAP-A)

  • Gábor Molnár

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 protocols and procedures were performed according to the European Communities Council Directives of 1986 (86/609/EEC) and 2003 (2003/65/CE) for animal research and were approved by the Ethics Committee of the University of Szeged.

Human subjects: All procedures were performed according to the Declaration of Helsinki with the approval of the University of Szeged Ethical Committee. Informed consent, and consent to publish, was obtained from patients. The permit number for our human experiments is 75/2004 issued by the Human Investigation Review Board of the University of Szeged.

Copyright

© 2016, Molnár 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

  • 2,574
    views
  • 600
    downloads
  • 89
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

Share this article

https://doi.org/10.7554/eLife.18167

Further reading

    1. Neuroscience
    Sainan Liu, Jiepin Huang ... Yan Yang
    Research Article

    Social relationships guide individual behavior and ultimately shape the fabric of society. Primates exhibit particularly complex, differentiated, and multidimensional social relationships, which form interwoven social networks, reflecting both individual social tendencies and specific dyadic interactions. How the patterns of behavior that underlie these social relationships emerge from moment-to-moment patterns of social information processing remains unclear. Here, we assess social relationships among a group of four monkeys, focusing on aggression, grooming, and proximity. We show that individual differences in social attention vary with individual differences in patterns of general social tendencies and patterns of individual engagement with specific partners. Oxytocin administration altered social attention and its relationship to both social tendencies and dyadic relationships, particularly grooming and aggression. Our findings link the dynamics of visual information sampling to the dynamics of primate social networks.

    1. Neuroscience
    Sergio Casas-Tinto, Nuria Garcia-Guillen, María Losada-Perez
    Short Report

    As the global population ages, the prevalence of neurodegenerative disorders is fast increasing. This neurodegeneration as well as other central nervous system (CNS) injuries cause permanent disabilities. Thus, generation of new neurons is the rosetta stone in contemporary neuroscience. Glial cells support CNS homeostasis through evolutionary conserved mechanisms. Upon damage, glial cells activate an immune and inflammatory response to clear the injury site from debris and proliferate to restore cell number. This glial regenerative response (GRR) is mediated by the neuropil-associated glia (NG) in Drosophila, equivalent to vertebrate astrocytes, oligodendrocytes (OL), and oligodendrocyte progenitor cells (OPCs). Here, we examine the contribution of NG lineages and the GRR in response to injury. The results indicate that NG exchanges identities between ensheathing glia (EG) and astrocyte-like glia (ALG). Additionally, we found that NG cells undergo transdifferentiation to yield neurons. Moreover, this transdifferentiation increases in injury conditions. Thus, these data demonstrate that glial cells are able to generate new neurons through direct transdifferentiation. The present work makes a fundamental contribution to the CNS regeneration field and describes a new physiological mechanism to generate new neurons.