Electrical synapses are found in vertebrate and invertebrate nervous systems. The cellular basis of these synapses is the gap junction, a group of intercellular channels that mediate direct communication between adjacent neurons. Similar to chemical synapses, electrical connections are modifiable and their variations in strength provide a mechanism for reconfiguring neural circuits. In addition, electrical synapses dynamically regulate neural circuits through properties without equivalence in chemical transmission. Because of their continuous nature and bidirectionality, electrical synapses allow electrical currents underlying changes in membrane potential to leak to ‘coupled’ partners, dampening neuronal excitability and altering their integrative properties. Remarkably, this effect can be transiently alleviated when comparable changes in membrane potential simultaneously occur in each of the coupled neurons, a phenomenon that is dynamically dictated by the timing of arriving signals such as synaptic potentials. By way of this mechanism, electrical synapses influence synaptic integration and action potential generation, imparting an additional layer of dynamic complexity to neural circuits.
Subscribe to Journal
Get full journal access for 1 year
only $21.58 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Marx, K. & Martin, N. Grundrisse: Foundations of the Critique of Political Economy (Penguin, 1993).
Sheng, M., Sabatini, B. L. & Sudhof, T. The Synapse (Cold Spring Harbor Laboratory Press, 2012).
Agnati, L. F., Guidolin, D., Guescini, M., Genedani, S. & Fuxe, K. Understanding wiring and volume transmission. Brain Res. Rev. 64, 137–159 (2010).
Taber, K. H. & Hurley, R. A. Volume transmission in the brain: beyond the synapse. J. Neuropsychiatry Clin. Neurosci. 26, 1–4 (2014).
Connors, B. W. & Long, M. A. Electrical synapses in the mammalian brain. Annu. Rev. Neurosci. 27, 393–418 (2004).
Goodenough, D. a & Paul, D. L. Gap junctions. Cold Spring Harb. Perspect. Biol. 1, a002576 (2009).
Heifets, B. D. & Castillo, P. E. Endocannabinoid signaling and long-term synaptic plasticity. Annu. Rev. Physiol. 71, 283–306 (2009).
Martin, S. J., Grimwood, P. D. & Morris, R. G. M. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711 (2000).
Tritsch, N. X. & Sabatini, B. L. Dopaminergic modulation of synaptic transmission in cortex and striatum. Neuron 76, 33–50 (2012).
Cai, X. et al. Local potentiation of excitatory synapses by serotonin and its alteration in rodent models of depression. Nat. Neurosci. 16, 464–472 (2013).
Bloomfield, S. A. & Völgyi, B. The diverse functional roles and regulation of neuronal gap junctions in the retina. Nat. Rev. Neurosci. 10, 495–506 (2009). This review article provides a comprehensive view on the role of electrical synapses in retinal networks, a region of the CNS where the diversity and functional contributions of electrical synapses have been more extensively studied.
Zsiros, V. & Maccaferri, G. Noradrenergic modulation of electrical coupling in GABAergic networks of the hippocampus. J. Neurosci. 28, 1804–1815 (2008).
Johnson, B. R., Schneider, L. R., Nadim, F. & Harris-Warrick, R. M. Dopamine modulation of phasing of activity in a rhythmic motor network: contribution of synaptic and intrinsic modulatory actions. J. Neurophysiol. 94, 3101–3111 (2005).
Smith, M. & Pereda, A. E. Chemical synaptic activity modulates nearby electrical synapses. Proc. Natl Acad. Sci. USA 100, 4849–4854 (2003).
Kothmann, W. W. et al. Nonsynaptic NMDA receptors mediate activity-dependent plasticity of gap junctional coupling in the AII amacrine cell network. J. Neurosci. 32, 6747–6759 (2012).
Turecek, J. et al. NMDA receptor activation strengthens weak electrical coupling in mammalian brain. Neuron 81, 1375–1388 (2014).
Haas, J. S., Zavala, B. & Landisman, C. E. Activity-dependent long-term depression of electrical synapses. Science 334, 389–393 (2011).
Sevetson, J., Fittro, S., Heckman, E. & Haas, J. S. A calcium-dependent pathway underlies activity-dependent plasticity of electrical synapses in the thalamic reticular nucleus. J. Physiol. 595, 4417–4430 (2017).
Pereda, A. E. Electrical synapses and their functional interactions with chemical synapses. Nat. Rev. Neurosci. 15, 250–263 (2014).
Haas, J. S., Greenwald, C. M. & Pereda, A. E. Activity-dependent plasticity of electrical synapses: increasing evidence for its presence and functional roles in the mammalian brain. BMC Cell Biol. 17, 14 (2016).
Li, H., Chuang, A. Z. & O’Brien, J. Photoreceptor coupling is controlled by connexin 35 phosphorylation in zebrafish retina. J. Neurosci. 29, 15178–15186 (2009).
O’Brien, J. The ever-changing electrical synapse. Curr. Opin. Neurobiol. 29C, 64–72 (2014).
Herring, B. E. & Nicoll, R. A. Long-term potentiation: from CaMKII to AMPA receptor trafficking. Annu. Rev. Physiol. 78, 351–365 (2016).
Gaietta, G. et al. Multicolor and electron microscopic imaging of connexin trafficking. Science 296, 503–507 (2002).
Gumpert, A. M., Varco, J. S., Baker, S. M., Piehl, M. & Falk, M. M. Double-membrane gap junction internalization requires the clathrin-mediated endocytic machinery. FEBS Lett. 582, 2887–2892 (2008).
Wang, H. Y., Lin, Y.-P., Mitchell, C. K., Ram, S. & O’Brien, J. Two-color fluorescent analysis of connexin 36 turnover: relationship to functional plasticity. J. Cell Sci. 128, 3888–3897 (2015).
Laird, D. W. The life cycle of a connexin: gap junction formation, removal, and degradation. J. Bioenerg. Biomembr. 28, 311–318 (1996).
Flores, C. E. et al. Trafficking of gap junction channels at a vertebrate electrical synapse in vivo. Proc. Natl Acad. Sci. USA 109, E573–E582 (2012).
Piehl, M. et al. Internalization of large double-membrane intercellular vesicles by a clathrin-dependent endocytic process. Mol. Biol. Cell 18, 337–347 (2007).
Phelan, P. Innexins: members of an evolutionarily conserved family of gap-junction proteins. Biochim. Biophys. Acta 1711, 225–245 (2005).
Meng, L., Chen, C. & Yan, D. Regulation of gap junction dynamics by UNC-44/ankyrin and UNC-33/CRMP through VAB-8 in C. elegans neurons. PLOS Genet. 12, e1005948 (2016).
Lynn, B. D., Li, X. & Nagy, J. I. Under construction: building the macromolecular superstructure and signaling components of an electrical synapse. J. Membr. Biol. 245, 303–317 (2012).
Flores, C. E., Li, X., Bennett, M. V. L., Nagy, J. I. & Pereda, A. E. Interaction between connexin35 and zonula occludens-1 and its potential role in the regulation of electrical synapses. Proc. Natl Acad. Sci. USA 105, 12545–12550 (2008).
Miller, A. C., Voelker, L. H., Shah, A. N. & Moens, C. B. Neurobeachin is required postsynaptically for electrical and chemical synapse formation. Curr. Biol. 25, 16–28 (2015).
Miller, A. C. & Pereda, A. E. The electrical synapse: molecular complexities at the gap and beyond. Dev. Neurobiol. 77, 562–574 (2017).
Curti, S., Hoge, G., Nagy, J. I. & Pereda, A. E. Synergy between electrical coupling and membrane properties promotes strong synchronization of neurons of the mesencephalic trigeminal nucleus. J. Neurosci. 32, 4341–4359 (2012). The article shows the close functional relationship between intrinsic membrane properties and electrical transmission, in particular its frequency dependence.
Lin, J. W. & Faber, D. S. Synaptic transmission mediated by single club endings on the goldfish Mauthner cell. I. Characteristics of electrotonic and chemical postsynaptic potentials. J. Neurosci. 8, 1302–1312 (1988).
Rash, J. E. et al. Molecular and functional asymmetry at a vertebrate electrical synapse. Neuron 79, 957–969 (2013).
Szoboszlay, M. et al. Functional properties of dendritic gap junctions in cerebellar golgi cells. Neuron 90, 1043–1056 (2016).
Marandykina, A., Palacios-Prado, N., Rimkute, L., Skeberdis, V. A. & Bukauskas, F. F. Regulation of connexin36 gap junction channels by n-alkanols and arachidonic acid. J. Physiol. 591, 2087–2101 (2013).
Bennett, M. V. L. in The Handbook of Physiology (ed. Kandel, E.) 357–416 (American Physiological Society, 1977).
Forbes, M. S. & Sperelakis, N. Association between mitochondria and gap junctions in mammalian myocardial cells. Tissue Cell 14, 25–37 (1982).
Matthews, G. & Fuchs, P. The diverse roles of ribbon synapses in sensory neurotransmission. Nat. Rev. Neurosci. 11, 812–822 (2010).
Morales, F. R. & Chase, M. H. Repetitive synaptic potentials responsible for inhibition of spinal cord motoneurons during active sleep. Exp. Neurol. 78, 471–476 (1982).
Faure, P. & Korn, H. A nonrandom dynamic component in the synaptic noise of a central neuron. Proc. Natl Acad. Sci. USA 94, 6506–6511 (1997).
Farrant, M. & Nusser, Z. Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors. Nat. Rev. Neurosci. 6, 215–229 (2005).
Getting, P. A. Modification of neuron properties by electrotonic synapses. Input resistance, I. time constant, and integration. J. Neurophysiol. 37, 846–857 (1974). Combining experimental evidence and mathematical simulations, this seminal study formally describes the close functional interrelationship between electrical transmission and the passive properties of the neuron and the impact of electrical synapses on the integrative properties of the coupled cells.
Amitai, Y. et al. The spatial dimensions of electrically coupled networks of interneurons in the neocortex. J. Neurosci. 22, 4142–4152 (2002).
Alcami, P. & Marty, A. Estimating functional connectivity in an electrically coupled interneuron network. Proc. Natl Acad. Sci. USA 110, E4798–E4807 (2013). The article describes the contribution of all coupled neurons to C N and R N of a given neuron and the use of capacitive currents to estimate the number of neurons forming a coupled compartment.
Amsalem, O., Van Geit, W., Muller, E., Markram, H. & Segev, I. From neuron biophysics to orientation selectivity in electrically coupled networks of neocortical L2/3 large basket cells. Cereb. Cortex 26, 3655–3668 (2016). Using a detailed realistic model of neocortical interneurons, the authors of this paper show how electrical synapses dynamically influence the time window for integration of excitatory chemical events.
Deans, M. R., Gibson, J. R., Sellitto, C., Connors, B. W. & Paul, D. L. Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36. Neuron 31, 477–485 (2001).
Santos-Sacchi, J. Isolated supporting cells from the organ of Corti: some whole cell electrical characteristics and estimates of gap junctional conductance. Hear. Res. 52, 89–98 (1991).
Rall, W. Time constants and electrotonic length of membrane cylinders and neurons. Biophys. J. 9, 1483–1508 (1969).
Bennett, M. V. Physiology of electrotonic junctions. Ann. NY Acad. Sci. 137, 509–539 (1966). This seminal article formally describes the factors influencing the strength of electrical synapses, expressed as the steady-state CC.
Leznik, E. & Llinás, R. Role of gap junctions in synchronized neuronal oscillations in the inferior olive. J. Neurophysiol. 94, 2447–2456 (2005).
Lefler, Y., Yarom, Y. & Uusisaari, M. Y. Cerebellar inhibitory input to the inferior olive decreases electrical coupling and blocks subthreshold oscillations. Neuron 81, 1389–1400 (2014).
Spira, M. E., Spray, D. C. & Bennett, M. V. Electrotonic coupling: effective sign reversal by inhibitory neurons. Science 194, 1065–1067 (1976).
Devor, A. & Yarom, Y. Electrotonic coupling in the inferior olivary nucleus revealed by simultaneous double patch recordings. J. Neurophysiol. 87, 3048–3058 (2002).
Landisman, C. E. et al. Electrical synapses in the thalamic reticular nucleus. J. Neurosci. 22, 1002–1009 (2002).
Hoge, G. J. et al. The extent and strength of electrical coupling between inferior olivary neurons is heterogeneous. J. Neurophysiol. 105, 1089–1101 (2011).
Galarreta, M. & Hestrin, S. Electrical synapses between GABA-releasing interneurons. Nat. Rev. Neurosci. 2, 425–433 (2001).
Vervaeke, K. et al. Rapid desynchronization of an electrically coupled interneuron network with sparse excitatory synaptic input. Neuron 67, 435–451 (2010).
Kothmann, W. W., Massey, S. C. & O’Brien, J. Dopamine-stimulated dephosphorylation of connexin 36 mediates AII amacrine cell uncoupling. J. Neurosci. 29, 14903–14911 (2009).
Dugué, G. P. et al. Electrical coupling mediates tunable low-frequency oscillations and resonance in the cerebellar Golgi cell network. Neuron 61, 126–139 (2009). The authors show how the spike AHP efficiently propagates between cerebellar Golgi cells via electrical synapses to influence their properties.
Galarreta, M. & Hestrin, S. A network of fast-spiking cells in the neocortex connected by electrical synapses. Nature 402, 72–75 (1999).
Zsiros, V., Aradi, I. & Maccaferri, G. Propagation of postsynaptic currents and potentials via gap junctions in GABAergic networks of the rat hippocampus. J. Physiol. 578, 527–544 (2007).
Pereda, A. E., Rash, J. E., Nagy, J. I. & Bennett, M. V. L. Dynamics of electrical transmission at club endings on the Mauthner cells. Brain Res. Brain Res. Rev. 47, 227–244 (2004).
Llinás, R. R. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 242, 1654–1664 (1988). This influential review article argues that the diversity of membrane-intrinsic properties in neurons is a main contributor to the function of the nervous system.
Mann-Metzer, P. & Yarom, Y. Electrotonic coupling interacts with intrinsic properties to generate synchronized activity in cerebellar networks of inhibitory interneurons. J. Neurosci. 19, 3298–3306 (1999). The authors show how the synchrony between cerebellar molecular layer interneurons is enhanced by the boosting of spikelets by a subthreshold Na + conductance.
Curti, S. & Pereda, A. E. Voltage-dependent enhancement of electrical coupling by a subthreshold sodium current. J. Neurosci. 24, 3999–4010 (2004).
Haas, J. S. & Landisman, C. E. State-dependent modulation of gap junction signaling by the persistent sodium current. Front. Cell. Neurosci. 5, 31 (2011).
Pereda, A. E. et al. Gap junction-mediated electrical transmission: regulatory mechanisms and plasticity. Biochim. Biophys. Acta 1828, 134–146 (2013).
Hutcheon, B. & Yarom, Y. Resonance, oscillation and the intrinsic frequency preferences of neurons. Trends Neurosci. 23, 216–222 (2000).
Izhikevich, E. M. Dynamical Systems in Neuroscience: the Geometry of Excitability and Bursting (MIT Press, 2007).
Stafstrom, C. E., Schwindt, P. C., Chubb, M. C. & Crill, W. E. Properties of persistent sodium conductance and calcium conductance of layer V neurons from cat sensorimotor cortex in vitro. J. Neurophysiol. 53, 153–170 (1985).
Apostolides, P. F. & Trussell, L. O. Control of interneuron firing by subthreshold synaptic potentials in principal cells of the dorsal cochlear nucleus. Neuron 83, 324–330 (2014).
Alcami, P. Electrical synapses enhance and accelerate interneuron recruitment in response to coincident and sequential excitation. Front. Cell. Neurosci. 12, 156 (2018).
Veruki, M. L. & Hartveit, E. AII (Rod) amacrine cells form a network of electrically coupled interneurons in the mammalian retina. Neuron 33, 935–946 (2002). The article is the first to show coincidence detection of depolarizations in retinal networks.
Getting, P. A. & Willows, A. O. Modification of neuron properties by electrotonic synapses. II. Burst formation by electrotonic synapses. J. Neurophysiol. 37, 858–868 (1974).
Krahe, R. & Gabbiani, F. Burst firing in sensory systems. Nat. Rev. Neurosci. 5, 13–23 (2004).
Manookin, M. B., Patterson, S. S. & Linehan, C. M. Neural mechanisms mediating motion sensitivity in parasol ganglion cells of the primate retina. Neuron 97, 1327–1340 (2018).
Murphy-Baum, B. L. & Awatramani, G. B. An old neuron learns new tricks: redefining motion processing in the primate retina. Neuron 97, 1205–1207 (2018).
Rörig, B., Klausa, G. & Sutor, B. Intracellular acidification reduced gap junction coupling between immature rat neocortical pyramidal neurones. J. Physiol. 490, 31–49 (1996).
Rall, W., Burke, R. E., Smith, T. G., Nelson, P. G. & Frank, K. Dendritic location of synapses and possible mechanisms for the monosynaptic EPSP in motoneurons. J. Neurophysiol. 30, 1169–1193 (1967).
Mejia-Gervacio, S. et al. Axonal speeding: shaping synaptic potentials in small neurons by the axonal membrane compartment. Neuron 53, 843–855 (2007).
Nörenberg, A., Hu, H., Vida, I., Bartos, M. & Jonas, P. Distinct nonuniform cable properties optimize rapid and efficient activation of fast-spiking GABAergic interneurons. Proc. Natl Acad. Sci. USA 107, 894–899 (2010).
Rela, L. & Szczupak, L. Gap junctions: their importance for the dynamics of neural circuits. Mol. Neurobiol. 30, 341–358 (2004).
Vazquez, Y., Mendez, B., Trueta, C. & De-Miguel, F. F. Summation of excitatory postsynaptic potentials in electrically-coupled neurones. Neuroscience 163, 202–212 (2009).
Galarreta, M. & Hestrin, S. Spike transmission and synchrony detection in networks of GABAergic interneurons. Science 292, 2295–2299 (2001). The article shows the mechanisms by which electrical synapses mediate coincidence detection in a network of neocortical interneurons.
Yaeger, D. & Trussell, L. O. Auditory Golgi cells are interconnected predominantly by electrical synapses. J. Neurophysiol. 116, 540–551 (2016).
Hjorth, J., Blackwell, K. T. & Kotaleski, J. H. Gap junctions between striatal fast-spiking interneurons regulate spiking activity and synchronization as a function of cortical activity. J. Neurosci. 29, 5276–5286 (2009). In a model of coupled striatal interneurons, the authors show that the addition of electrical synapses reduces overall firing when the network is excited by poorly correlated inputs and that this effect is alleviated when the network is excited with highly correlated inputs.
Nath, A. & Schwartz, G. W. Electrical synapses convey orientation selectivity in the mouse retina. Nat. Commun. 8, 2025 (2017).
Roy, K., Kumar, S. & Bloomfield, S. A. Gap junctional coupling between retinal amacrine and ganglion cells underlies coherent activity integral to global object perception. Proc. Natl Acad. Sci. USA 114, E10484–E10493 (2017).
Bennett, M. V. L., Crain, S. M. & Grundfest, H. Patterns of response and neural organization of supramedullary neurons of puffer (blowfish), Spheroides maculatus. Biol. Bull. 1957, 325–326 (1957).
Connors, B. W. Synchrony and so much more: diverse roles for electrical synapses in neural circuits. Dev. Neurobiol. 77, 610–624 (2017).
Wu, N., Hsiao, C. F. & Chandler, S. H. Membrane resonance and subthreshold membrane oscillations in mesencephalic V neurons: participants in burst generation. J. Neurosci. 21, 3729–3739 (2001).
Placantonakis, D. G., Bukovsky, A. A., Aicher, S. A., Kiem, H.-P. & Welsh, J. P. Continuous electrical oscillations emerge from a coupled network: a study of the inferior olive using lentiviral knockdown of connexin36. J. Neurosci. 26, 5008–5016 (2006). The article provides direct evidence for the association of electrical coupling with subthreshold network oscillations.
Placantonakis, D. G., Bukovsky, A. A., Zeng, X.-H., Kiem, H.-P. & Welsh, J. P. Fundamental role of inferior olive connexin 36 in muscle coherence during tremor. Proc. Natl Acad. Sci. USA 101, 7164–7169 (2004).
Long, M. A., Deans, M. R., Paul, D. L. & Connors, B. W. Rhythmicity without synchrony in the electrically uncoupled inferior olive. J. Neurosci. 22, 10898–10905 (2002).
Chen, Y., Li, X., Rotstein, H. G. & Nadim, F. Membrane potential resonance frequency directly influences network frequency through electrical coupling. J. Neurophysiol. 116, 1554–1563 (2016).
Hestrin, S. & Galarreta, M. Electrical synapses define networks of neocortical GABAergic neurons. Trends Neurosci. 28, 304–309 (2005).
Gutierrez, G. J. & Marder, E. Rectifying electrical synapses can affect the influence of synaptic modulation on output pattern robustness. J. Neurosci. 33, 13238–13248 (2013).
Gutierrez, G. J. & Marder, E. Modulation of a single neuron has state-dependent actions on circuit dynamics. eNeuro https://doi.org/10.1523/ENEURO.0009-14.2014 (2014).
Traub, R. D., Whittington, M. A., Gutiérrez, R. & Draguhn, A. Electrical coupling between hippocampal neurons: contrasting roles of principal cell gap junctions and interneuron gap junctions. Cell Tissue Res. 373, 671–691 (2018).
Marder, E., Gutierrez, G. J. & Nusbaum, M. P. Complicating connectomes: electrical coupling creates parallel pathways and degenerate circuit mechanisms. Dev. Neurobiol. 77, 597–609 (2017). This review article exposes a number of non-intuitive network dynamics mediated by electrical synapses in reduced networks of the STG.
O’Brien, J. & Bloomfield, S. A. Plasticity of retinal gap junctions: roles in synaptic physiology and disease. Annu. Rev. Vis. Sci. 4, 79–100 (2018).
Pernelle, G., Nicola, W. & Clopath, C. Gap junction plasticity as a mechanism to regulate network-wide oscillations. PLOS Comput. Biol. 14, e1006025 (2018).
Palacios-Prado, N., Huetteroth, W. & Pereda, A. E. Hemichannel composition and electrical synaptic transmission: molecular diversity and its implications for electrical rectification. Front. Cell. Neurosci. 8, 324 (2014).
Zhang, W. & Linden, D. J. The other side of the engram: experience-driven changes in neuronal intrinsic excitability. Nat. Rev. Neurosci. 4, 885–900 (2003).
Aizenman, C. D. & Linden, D. J. Rapid, synaptically driven increases in the intrinsic excitability ofcerebellar deep nuclear neurons. Nat. Neurosci. 3, 109–111 (2000).
Turrigiano, G., Abbott, L. F. & Marder, E. Activity-dependent changes in the intrinsic properties of cultured neurons. Science 264, 974–977 (1994).
Carew, T. J. & Kandel, E. R. Two functional effects of decreased conductance EPSP’s: synaptic augmentation and increased electrotonic coupling. Science 192, 150–153 (1976).
Trenholm, S., McLaughlin, A. J., Schwab, D. J. & Awatramani, G. B. Dynamic tuning of electrical and chemical synaptic transmission in a network of motion coding retinal neurons. J. Neurosci. 33, 14927–14938 (2013). The paper shows how dynamic interactions between electrical and chemical synapses and intrinsic membrane properties allow a direction-selective retinal network to propagate anticipatory responses effectively along its preferred direction.
Marder, E. & Bucher, D. Understanding circuit dynamics using the stomatogastric nervous system of lobsters and crabs. Annu. Rev. Physiol. 69, 291–316 (2007).
Lane, B. J., Samarth, P., Ransdell, J. L., Nair, S. S. & Schulz, D. J. Synergistic plasticity of intrinsic conductance and electrical coupling restores synchrony in an intact motor network. eLife 5, e16879 (2016).
Marder, E. Neuromodulation of neuronal circuits: back to the future. Neuron 76, 1–11 (2012).
Rieubland, S., Roth, A. & Häusser, M. Structured connectivity in cerebellar inhibitory networks. Neuron 81, 913–929 (2014).
Bartos, M. et al. Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks. Proc. Natl Acad. Sci. USA 99, 13222–13227 (2002).
Zhang, B. et al. Action potential-triggered somatic exocytosis in mesencephalic trigeminal nucleus neurons in rat brain slices. J. Physiol. 590, 753–762 (2012).
Isaacson, J. S. & Strowbridge, B. W. Olfactory reciprocal synapses: dendritic signaling in the CNS. Neuron 20, 749–761 (1998).
Fukuda, T. & Kosaka, T. Ultrastructural study of gap junctions between dendrites of parvalbumin-containing GABAergic neurons in various neocortical areas of the adult rat. Neuroscience 120, 5–20 (2003).
Fukuda, T. Network architecture of gap junction-coupled neuronal linkage in the striatum. J. Neurosci. 29, 1235–1243 (2009).
Sloper, J. J. Gap junctions between dendrites in the primate neocortex. Brain Res. 44, 641–646 (1972).
Sotelo, C., Llinas, R. & Baker, R. Structural study of inferior olivary nucleus of the cat: morphological correlates of electrotonic coupling. J. Neurophysiol. 37, 541–559 (1974).
Nagy, J. I., Pereda, A. E. & Rash, J. E. Electrical synapses in mammalian CNS: past eras, present focus and future directions. Biochim. Biophys. Acta Biomembr. 1860, 102–123 (2018).
Hormuzdi, S. G. et al. Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice. Neuron 31, 487–495 (2001).
Steriade, M. Synchronized activities of coupled oscillators in the cerebral cortex and thalamus at different levels of vigilance. Cereb. Cortex 7, 583–604 (1997).
Moghaddam, B. Bringing order to the glutamate chaos in schizophrenia. Neuron 40, 881–884 (2003).
Hammond, C., Bergman, H. & Brown, P. Pathological synchronization in Parkinson’s disease: networks, models and treatments. Trends Neurosci. 30, 357–364 (2007).
Vervaeke, K., Lorincz, A., Nusser, Z. & Silver, R. A. Gap junctions compensate for sublinear dendritic integration in an inhibitory network. Science 335, 1624–1628 (2012). The article shows how communication between distal portions of dendrites via electrical synapses allows remotely located inputs to efficiently drive the network of cerebellar Golgi cells.
Trenholm, S. et al. Nonlinear dendritic integration of electrical and chemical synaptic inputs drives fine-scale correlations. Nat. Neurosci. 17, 1759–1766 (2014).
Pappas, G. D. & Bennett, M. V. Specialized junctions involved in electrical transmission between neurons. Ann. NY Acad. Sci. 137, 495–508 (1966).
Baker, R. & Llinás, R. Electrotonic coupling between neurones in the rat mesencephalic nucleus. J. Physiol. 212, 45–63 (1971).
Sotelo, C. & Llinás, R. Specialized membrane junctions between neurons in the vertebrate cerebellar cortex. J. Cell Biol. 53, 271–289 (1972).
Gahr, M. & Garcia-Segura, L. M. Testosterone-dependent increase of gap-junctions in HVC neurons of adult female canaries. Brain Res. 712, 69–73 (1996).
Hamzei-Sichani, F. et al. Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze fracture replica immunogold labeling. Proc. Natl Acad. Sci. USA 104, 12548–12553 (2007).
Schmitz, D. et al. Axo-axonal coupling. a novel mechanism for ultrafast neuronal communication. Neuron 31, 831–840 (2001).
Draguhn, A., Traub, R. D., Schmitz, D. & Jefferys, J. G. R. Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro. Nature 394, 189–192 (1998).
Simon, A. et al. Gap junction networks can generate both ripple-like and fast ripple-like oscillations. Eur. J. Neurosci. 39, 46–60 (2014).
Roopun, A. K. et al. A nonsynaptic mechanism underlying interictal discharges in human epileptic neocortex. Proc. Natl Acad. Sci. USA 107, 338–343 (2010).
Wang, S., Borst, A., Zaslavsky, N., Tishby, N. & Segev, I. Efficient encoding of motion is mediated by gap junctions in the fly visual system. PLOS Comput. Biol. 13, e1005846 (2017).
Nagy, J. I., Pereda, A. E. & Rash, J. E. On the occurrence and enigmatic functions of mixed (chemical plus electrical) synapses in the mammalian CNS. Neurosci. Lett. https://doi.org/10.1016/j.neulet.2017.09.021 (2017).
Sabatini, B. L. & Regehr, W. G. Timing of neurotransmission at fast synapses in the mammalian brain. Nature 384, 170–172 (1996).
Pereda, a E., Bell, T. D. & Faber, D. S. Retrograde synaptic communication via gap junctions coupling auditory afferents to the Mauthner cell. J. Neurosci. 15, 5943–5955 (1995).
Herberholz, J., Antonsen, B. L. & Edwards, D. H. A lateral excitatory network in the escape circuit of crayfish. J. Neurosci. 22, 9078–9085 (2002).
Song, J., Ampatzis, K., Björnfors, E. R. & El Manira, A. Motor neurons control locomotor circuit function retrogradely via gap junctions. Nature 529, 399–402 (2016). The article shows the impact of motor neuron activity on locomotor circuit function mediated retrogradely via gap junctions present at mixed, electrical and chemical synapses, belonging to spinal interneurons.
Korn, H., Sotelo, C. & Crepel, F. Electronic coupling between neurons in the rat lateral vestibular nucleus. Exp. Brain Res. 16, 255–275 (1973).
Cajal, S. R. y. Significación fisiológica de las expansiones protoplásmicas y nerviosas de las células de la sustancia gris [Spanish]. Rev. Cienc. Méd. Barc. 27, (1–5 (1891).
Eisen, J. S. & Marder, E. Mechanisms underlying pattern generation in lobster stomatogastric ganglion as determined by selective inactivation of identified neurons. III. Synaptic connections of electrically coupled pyloric neurons. J. Neurophysiol. 48, 1392–1415 (1982). This seminal article describes the non-intuitive network properties of electrical synapses, including the ambiguity in the analysis of network connectivity that originates from the coexistence of chemical and electrical synapses.
Lee, S.-C., Cruikshank, S. J. & Connors, B. W. Electrical and chemical synapses between relay neurons in developing thalamus. J. Physiol. 588, 2403–2415 (2010).
The authors thank D. S. Faber and A. Marty for valuable comments on the manuscript. The authors are indebted to the 2013 Grass Laboratory for the stimulating environment. The authors are supported by the Grass Foundation, the Munich Center for NeuroSciences (P.A.) and US National Institutes of Health grants DC03186, DC011099, NS055726, NS085772 and NS0552827 (A.E.P.).
Nature Reviews Neuroscience thanks G. Awatramani, E. Marder and M. Veruki for their contribution to the peer review of this work.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- Neurons of the mesencephalic nucleus of the trigeminus
Neurons of the mesencephalic nucleus of the trigeminus (MesV) are a class of primary afferents that innervate the spindles of jaw closer muscles and mechanoreceptors of periodontal ligaments. Unlike their counterparts in sensory ganglia, their large unipolar somata are located within the CNS and are distributed within the brainstem.
- Cerebellar Golgi cells
Golgi cells are local inhibitory interneurons in the granule cell layer of the cerebellum. They regulate input signals to the cerebellar cortex by inhibiting granule cells.
- Mauthner cells
A pair of large reticulospinal medullary neurons that mediate sensory-evoked escape responses in fish.
- Amacrine type AII cells
Amacrine cells are a class of retinal interneurons. Type AII amacrine cells relay information originated in rod photoreceptors through the ON centre cone bipolar axons to ON centre ganglion cells by way of electrical synapses.
- Coincidence detection
The term coincidence detection is used to describe a process by which neurons or neural circuits are capable of encoding information by detecting the occurrence of temporally close signals.
- Retzius cells
Retzius cells are two large serotoninergic neurons present at each of the 21 segmental ganglia of the leech (Hirudo medicinalis) nervous system. They are involved in swimming, bending and learning behaviours.
- Stomatogastric ganglion
(STG). The STG represents a group of near 30 neurons located on the stomach of decapod crustaceans, which control its rhythmic motor behaviour. These neurons are organized in two central pattern generators, pyloric and gastric, responsible for dilation and constriction of the pyloric region and chewing, respectively.
- HVC nucleus
The HVC (formerly ‘high vocal centre’) is a premotor nucleus in the brain of songbirds that has a key role in song production. It contains neurons that encode timing during the song.
- Law of dynamic polarization
Introduced by Ramón y Cajal, the neuron doctrine argues that the individual neuron is the unit of structure and function of the nervous system. Adding to this notion, the law of dynamic polarization postulates the presence of a unidirectional flow of information within neurons, from their dendrites (input region) and cell bodies to the axons, which constitute their output region.
About this article
Cite this article
Alcamí, P., Pereda, A.E. Beyond plasticity: the dynamic impact of electrical synapses on neural circuits. Nat Rev Neurosci 20, 253–271 (2019). https://doi.org/10.1038/s41583-019-0133-5
Effects of Propofol on Electrical Synaptic Strength in Coupling Reticular Thalamic GABAergic Parvalbumin-Expressing Neurons
Frontiers in Neuroscience (2020)
Differential Contribution of Gap Junctions to the Membrane Properties of ON- and OFF-Bipolar Cells of the Rat Retina
Cellular and Molecular Neurobiology (2020)
Neuromorphic Engineering for Hardware Computational Acceleration and Biomimetic Perception Motion Integration
Advanced Intelligent Systems (2020)
The Journal of Physiology (2020)
Noise-Induced Synchronization and Antiresonance in Interacting Excitable Systems: Applications to Deep Brain Stimulation in Parkinson’s Disease
Physical Review X (2020)