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Licensed Unlicensed Requires Authentication Published by De Gruyter July 22, 2014

Wiring prior to firing: the evolutionary rise of electrical and chemical modes of synaptic transmission

  • Saak V. Ovsepian EMAIL logo and Nikolai P. Vesselkin EMAIL logo


Paracrine signaling and coupling via intercellular conduits are widely utilized for cell-cell interactions from primitive eukaryotes to advanced metazoa. Here, we review the functional and molecular data suggestive of a phylogenic continuum between these primeval forms of communication with the chemical and electrical synaptic transmission of neurons. We discuss selective evidence for the essential role played by the shift of function in early cellular morphologies and protosynaptic scaffolds, with their co-optation for new functionality, which ultimately lead to the rise of the chemical synapse. It is proposed that, rather than representing a transitional element, mixed electrochemical synapses exemplify an exaptive effect. The nonadaptive model of the synaptic origin described herein supports the pluralistic hypothesis of evolutionary change.

Corresponding authors: Saak V. Ovsepian, Department of Translational Brain Research, German Center for Neurodegenerative Diseases (DZNE), 81377 Munich, Germany; and Department of Biotechnology and International Centre for Neurotherapeutics, Dublin City University, Dublin 9, Ireland, e-mail: ; and Nikolai P. Vesselkin, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194021 St. Petersburg, Russia; and Faculty of Medicine, The State University of Saint Petersburg, 199034 St. Petersburg, Russia, e-mail:


The authors thank Drs. Valerie O’Leary and Hovik Panosyan and Prof. J. Oliver Dolly for insightful discussions and critical reading of the manuscript. This work was supported by the Neuroscience Section of the Programme for Research in Third Level Institutions (PRTLI) Cycle 4 (to S.V.O.) and RFFI-Grant N10098 (to N.P.V.). The PRTLI is cofunded through the European Regional Development Fund (ERDF), part of the European Union Structural Funds Programme 2007 to 2013.


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Received: 2014-5-22
Accepted: 2014-6-16
Published Online: 2014-7-22
Published in Print: 2014-12-1

©2014 by De Gruyter

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