E.P. thanks the Philippe and Bettencourt-Schueller Foundations. A.C.L. and S.L. are supported by a Sir Henry Wellcome Postdoctoral Fellowship and an EMBO Long-Term Fellowship, respectively. S.W. is funded by a Wellcome Trust Senior Research Fellowship in the Basic Biomedical Sciences, grant MH081982 from the National Institutes 5-Fluoracil of Health, and by funds from the Gatsby Charitable Foundation and Oxford Martin School. “
“While the physiological importance of electrical synaptic transmission

in cold-blooded vertebrates has long been established (Bennett, 1977), progress over the last decade has also revealed the widespread distribution of electrical synapses, and this modality of synaptic transmission was reported to underlie important functional processes in diverse regions of the mammalian CNS (Connors and Long, 2004). Consequently, electrical transmission is now considered an essential form of interneuronal communication that, together with chemical transmission, dynamically distributes the processing of information within neural networks. In contrast to detailed knowledge of the mechanisms underlying chemical transmission, far less is known about how the

molecular architecture or the potentially diverse biophysical properties of electrical synapses encountered in physiologically Navitoclax solubility dmso disparate neural systems govern their function or impact on characteristics of electrical transmission most in those systems. Electrical synaptic transmission is mediated by clusters of intercellular channels that are assembled as gap junctions (GJs). Each intercellular channel is formed by the

docking of two hexameric connexin hemichannels (or connexons), which are individually contributed by each of the adjoining cells, forming molecular pathways for the direct transfer of signaling molecules and for the spread of electrical currents between cells. As a result, electrical synapses are often perceived as symmetrical structures, at which pre- and postsynaptic sites are viewed as the mirror image of each other. Connexons are formed by proteins called connexins that are the products of a multigene family that is unique to chordates (Cruciani and Mikalsen, 2007). Because of its widespread expression in neurons, connexin 36 (Cx36) is considered the main “synaptic” connexin in mammals. In contrast to other connexins, such as some found in glia (Yum et al., 2007 and Orthmann-Murphy et al., 2007), all pairing configurations tested so far indicate that Cx36 forms only “homotypic” intercellular channels (Teubner et al., 2000 and Li et al., 2004), where connexons composed of Cx36 pair only with apposing Cx36-containing connexons. Notably, the number of neuronal connexins is higher in teleost fishes, which, as a result of a genome duplication (Volff, 2005), have more than one homolog gene for most mammalian connexins (Eastman et al., 2006).