REVIEW Electrical coupling between hippocampal neurons: contrasting roles of principal cell gap junctions and interneuron gap junctions Roger D. Traub 1 & Miles A. Whittington 2 & Rafael Gutiérrez 3,4 & Andreas Draguhn 4 Received: 27 December 2017 /Accepted: 3 July 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract There is considerable experimental evidence, anatomical and physiological, that gap junctions exist in the hippocampus. Electrical coupling through these gap junctions may be divided into three types: between principal neurons, between interneurons and at mixed chemical (glutamatergic)/electrical synapses. An approach, combining in vitro experimental with modeling tech- niques, sheds some light on the functional consequences of electrical coupling, for network oscillations and for seizures. Additionally, in vivo experiments, using mouse connexin knockouts, suggest that the presence of electrical coupling is important for optimal performance on selected behavioral tasks; however, the interpretation of such data, in cellular terms, has so far proven difficult. Given that invertebrate central pattern generators so often depend on both chemical and electrical synapses, our hypothesis is that hippocampus-mediated and -influenced behaviors will act likewise. Experiments, likely hard ones, will be required to test this intuition. Keywords Gap junction . Axonal coupling . Dendritic coupling . Fast oscillation . Connexin45 . Connexin36 Introduction Multicellular organisms depend on the ability of different cells to communicate with one another. Indeed, even single-celled organisms sometimes join together for the exchange of genes (Adelberg and Pittard 1965). Gap junctions (Fig. 1) are one of the many schemes that Nature has evolved for such communication. They are not confined to nervous systems, rather being found in multiple tissues; in some of these tissues, such as the heart, gap junctions are absolutely essential to life. Concerning nervous systems, however, it would seem that gap junctions must also play a vital role: gap junctions occur in central pattern generators (Jing et al. 2011; Li et al. 2009; Marder and Eisen 1984) and other circuits (Furshpan and Potter 1959). They are present in many portions of vertebrate brains, spinal cord and retinas—yet invertebrates and verte- brates construct their gap junctions out of quite different clas- ses of protein: innexins versus connexins (and perhaps pannexins), suggesting convergent evolution of some vital biological element. Gap junctions in nervous systems are also phylogenetically extremely old (Takaku et al. 2014); preser- vation of such an ancient form of communication again sug- gests one or more crucial functions. Within the vertebrate CNS, most communication between neurons occurs through chemical synapses. Is it possible that gap junctions between neurons play a subordinate role and can, to first approximation, be ignored? We shall argue here that, on the contrary, gap junctions in the hippocampus play roles that are central to brain function. In order to make this case, we shall first review more elementary properties of gap junctions, such as their structure and location and the implica- tions of electrical coupling between pairs of neurons. Our * Roger D. Traub rtraub@us.ibm.com Rafael Gutiérrez rafagut@cinvestav.mx Andreas Draguhn andreas.draguhn@physiologie.uni-heidelberg.de 1 Department of Physical Sciences, IBM T.J. Watson Research Center, Yorktown Heights, NY 10598, USA 2 Hull York Medical School, University of York, Heslington YO10 5DD, UK 3 Department of Pharmacobiology, Centro de Investigación y de Estudios Avanzados del IPN, Calzada de los Tenorios 235, 14330 Mexico City, Mexico 4 Institut für Physiologie und Pathophysiologie, Universität Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg, Germany Cell and Tissue Research https://doi.org/10.1007/s00441-018-2881-3