Expression and functions of neuronal gap junctions

Nature Reviews Neuroscience

Volumn 6, Issue 3, 2005, Pages 191-200

  Söhl, Goran ^a   Maxeiner, Stephan ^a   Willecke, Klaus ^a  

^a UNIVERSITY OF BONN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CONNEXIN 36; CONNEXIN 45; CONNEXIN 57; GAP JUNCTION PROTEIN; PANNEXIN 1; PANNEXIN 2; UNCLASSIFIED DRUG;

BRAIN; CELL MEMBRANE; GAP JUNCTION; GENETIC DISORDER; HUMAN; MOUSE MUTANT; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; REVIEW; SYNAPSE;

ANIMALS; BRAIN; CELL COMMUNICATION; CONNEXINS; GAP JUNCTIONS; GENE EXPRESSION REGULATION; MODELS, NEUROLOGICAL; NERVE TISSUE PROTEINS; NEURONS; RETINA;

MAMMALIA; MURINAE;

EID: 14844295525     PISSN: 1471003X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrn1627     Document Type: Review

References (109)

1. Bennett, M. V. L. in Handbook of Physiology Sect. I Vol. 1 (ad. Kandel, E. R.) 357-416 (Williams and Wilkins, Baltimore, Maryland, 1977).
2. Kumar, N. M. & Gilula, N. B. The gap junction communication channel. Cell 84, 381-388 (1996).
3. Söhl, G. & Willecke, K. An update on connexin genes and their nomenclature in mouse and man. Cell Commun. Adhes. 10, 173-180 (2003).
4. Söhl, G., Odermatt, B., Maxeiner, S., Degen, J. & Willecke, K. New insights into the expression and function of neural connexins with transgenic mouse mutant. Brain Res. Brain Res. Rev. 47, 245-259 (2004).
5. Evans, W. H. & Martin, P. E. Gap junctions: structure and function (Review). Mol. Membr. Biol. 19, 121-136 (2002).
6. Lampe, P. D. & Lau, A. F. Regulation of gap junctions by phosphorylation of connexins. Arch. Biochem. Biophys. 384, 205-215 (2000).
7. Lampe, P. D. & Lau, A. F. The effects of connexin phosphorylation on gap junctional communication. Int. J. Biochem. Cell Biol. 36, 1171-1186 (2004).
8. Nagy, J. I., Dudek, F. E. & Rash, J. E. Update on connexins and gap junctions in neurons and glia in the mammalian nervous system. Brain Res. Brain Res. Rev. 47, 191-215 (2004).
9. Furshpan, E. J. & Potter, D. D. Transmission at the giant motor synapses of the crayfish. J. Physiol. (Lond.) 145, 289-325 (1959).
10. Korn, H., Sotelo, C. & Crepel, F. Electronic coupling between neurons in the rat lateral vestibular nucleus. Exp. Brain Res. 16, 255-275 (1973).
11. Connors, B. W. & Long, M. A. Electrical synapses in the mammalian brain. Annu. Rev. Neurosci. 27, 393-418 (2004).
12. Bennett, M. V. & Zukin, R. S. Electrical coupling and neuronal synchronization in the mammalian brain. Neuron 41, 495-511 (2004). Provides a comprehensive explanation and definition of low-pass filter characteristics.
13. Hormuzdi, S. G., Filippov, M. A., Mitropoulou, G., Monyer, H. & Bruzzone, R. Electrical synapses: a dynamic signaling system that shapes the activity of neuronal networks. Biochim. Biophys. Acta 1662, 113-137 (2004).
14. Alvarez-Maubeoin, V., Garcia-Hernandez, F., Williams, J. T. & Van Bockstaele, E. J. Functional coupling between neurons and glia. J. Neurosci. 20, 4091-4098 (2000).
15. Pakhotin, P. & Verkhratsky, A. Electrical synapses between Bergmann glia cells and Purkinje neurons in rat cerebellar slices. Mol. Cell. Neurosci. 28, 79-84 (2005).
16. Gibson, J. R., Beierlein, M. & Connors, B. W. Functional properties of electrical synapses between inhibitory interneurons of neocortical layer 4. J. Neurophysiol. 93, 467-480 (2005).
17. Buzsaki, G. & Chrobak, J. J. Temporal structure in spatially organized neuronal ensembles; a role for interneuronal networks. Curr. Opin. Neurobiol. 5, 504-510 (1995).
18. Fricker, D. & Miles, R. Interneurons, spike timing, and perception. Neuron 32, 771-774 (2001).
19. Smith, M. & Pereda, A. E. Chemical synaptic activity modulates nearby electrical synapses. Proc. Natl Acad. Sci. USA 100, 4849-4854 (2003).
20. Pereda, A. E., Rash, J. E., Nagy, J. I. & Bennett, M. V. Dynamics of electrical transmission at club endings on the Mauthner cells. Brain Res. Brain Res. Rev. 47, 227-244 (2004).
21. Iacobas, D. A. et al. Sensitivity of the brain transcriptome to connexin ablation. Biochem. Biophys. Acta 22 Dec 2004 (doi: 10.1016/j.bbamem.2004.12.002) .
22. Filippov, M. A., Hormuzdi, S. G., Fuchs, E. C. & Monyer, H. A reporter allele for investigating connexin 26 gene expression in the mouse brain. Eur. J. Neurosci. 18, 3183-3192 (2003).
23. Söhl, G., Gûldenagel, M., Traub, O. & Willecke, K. Connexin expression in the retina. Brain Res. Brain Res. Rev. 32, 138-145 (2000).
24. Dermietzel, R. et al. Differential expression of three gap junction proteins in developing and mature brain tissues. Proc. Natl Acad. Sci. USA 24, 10148-10152 (1989).
25. Condorelli, D. F. et al. Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons. Eur. J. Neurosci. 10, 1202-1208 (1998).
26. Söhl, G., Degen, J., Teubner, B. & Willecke, K. The murine gap junction gene connexin36 is highly expressed in mouse retina and regulated during brain development. FEBS Lett. 428, 27-31 (1998).
27. Maxeiner, S. et al. Spatiotemporal transcription of connexin45 during brain development results in neuronal expression in adult mice. Neuroscience 119, 689-700 (2003).
28. Maxeiner, S. & Dedek, K. et al. Deletion of connexin45 in mouse retinal neurons disrupts rod/cone signaling pathway between All amacrine and ON cone bipolar cells and leads to impaired visual transmission. J. Neurosci. 25, 566-576 (2005). This study reports results that are similar to those obtained from CX36-deficient mice (see reference 35). Both CX36- and CX45-knockout studies indicate that CX36 and CX45 form heterotypic electrical synapses between All amacrine and ON cone bipolar cells.
29. Hombach, S. et al. Functional expression of connexin57 in horizontal cells of the mouse retina. Eur. J. Neurosci. 19, 2633-2640 (2004).
30. Bruzzone, R., Hormuzdi, S. G., Barbe, M. T., Herb, A. & Monyer, H. Pannexins, a family of gap junction proteins expressed in brain. Proc. Natl Acad. Sci. USA 100, 13644-13649 (2003).
31. Condorelli, D. F., Belluardo, N., Trovato-Salinaro, A. & Mudo, G. Expression of Cx36 in mammalian neurons. Brain Res. Brain Res. Rev. 32, 72-85 (2000).
32. Belluardo, N. et al. Expression of connexin36 in the adult and developing rat brain. Brain Res. 19, 121-138 (2000).
33. Teubner, B. et al. Functional expression of the murine connexin36 gene coding for a neuron-specific gap junctional protein. J. Membr. Biol. 176, 249-262 (2000).
34. 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). Shows that rhythmic inhibitory potentials generated by low-threshold spiking interneurons of the neocortex could be induced, but show weak synchrony.
35. Güldenagel, M. et al. Visual transmission deficits in mice with targeted disruption of the gap junction gene connexin36. J. Neurosci. 21, 6035-6044 (2001). In this study, the disruption of the Cx36 gene led to a reduction of the b-wave and indicated that the heterologous gap junction coupling between All amacrine cells and ON cone bipolar cells is impaired in CX36-impaired mice.
36. Hormuzdi, S.G. et al. Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice. Neuron 31, 487-495 (2001). According to this report, targeted deletion of Cx36 does not abolish the gamma network oscillations but does reduce their synchrony and overall power.
37. Degen, J. et al. Expression pattern of lacZ reporter gene representing connexin36 in transgenic mice. J. Comp. Neurol. 473, 511-525 (2004).
38. 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).
39. Kistler W. M. et al. Analysis of Cx36 knockout does not support tenet that olivary gap junctions are required for complex spike synchronization and normal motor performance. Ann. NY Acad. Sci. 978, 391-404 (2002).
40. De Zeeuw, C. I. et al. Deformation of network connectivity in the inferior olive of connexin 36-deficient mice is compensated by morphological and electrophysiological changes at the single neuron level. J. Neurosci. 23, 4700-4711 (2003).
41. Frisch, C. et al. Memory impairment but no changes in brain cholinergic and monoaminergic levels after deletion of the neuronal gap junction protein connexin36 in mice. Behav. Brain Res. 157, 177-185 (2005).
42. Kistler, W. M. & DeZeeuw, C. I. Dynamical working memory and timed responses: the role of reverberating loops in the olivo-cerebellar system. Neural Comput. 14, 2597-2626 (2002).
43. 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).
44. 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).
45. Cheron, G. et al. Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the cerebellar cortex of alert mice. J. Neurosci. 24, 434-441 (2003).
46. Suzuki, W. A. Episodic memory signals in the rat hippocampus. Neuron 40, 1055-1056 (2003).
47. Dash, P. K., Hebert, A. E. & Runyan, J. D. A unified theory for systems and cellular memory consolidation. Brain Res. Brain Res. Rev. 45, 30-37 (2004).
48. Buzsaki, G., Buhl, D. L., Harris, K. D., Csicsvari, J., Czeh, B. & Morozov, A. Hippocampal network patterns of activity in the mouse. Neuroscience 116, 201-211 (2003).
49. Venance, L. et al. Connexin expression in electrically coupled postnatal rat brain neurons. Proc. Natl Acad. Sci. USA 97, 10260-10265 (2000).
50. Buhl, D. L., Harris, K. D., Hormuzdi, S. G., Monyer, H. & Buzsaki, G. Selective impairment of hippocampal gamma oscillations in connexin-36 knock-out mouse in vivo. J. Neurosci. 23, 1013-1018 (2003).
51. Maier, N. et al. Reduction of high-frequency network oscillations (ripples) and pathological network discharges in hippocampal slices from connexin 36-deficient mice. J. Physiol (Lond.). 541, 521-528 (2002).
52. Condorelli, D. F., Trovato-Salinaro, A., Mudo, G., Mirone, M. B. & Belluardo, N. Cellular expression of connexins in the rat brain: neuronal localization, effects of kainate-induced seizures and expression in apoptotic neuronal cells. Eur. J. Neurosci. 18, 1807-1827 (2003).
53. Panchin, Y. et al. A ubiquitous family of putative gap junction molecules. Curr. Biol. 10, R473-R474 (2000).
54. Bao, L., Locovei, S. & Dahl, G. Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett. 13, 65-68 (2004).
55. Traub, R. D. & Bibbig, A. A model of high-frequency ripples in the hippocampus based on synaptic coupling plus axon-axon gap junctions between pyramidal neurons. J. Neurosci. 20, 2086-2093 (2000).
56. Traub, R. D. et al. Axonal gap junctions between principal neurons: a novel source of network oscillations, and perhaps epileptogenesis. Rev. Neurosci. 13, 1-30 (2002).
57. Traub, R. D., Bibbig, A., LeBeau, F. E., Buhl, E. H. & Whittington, M. A. Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro. Annu. Rev. Neurosci. 27, 247-278 (2004).
58. Draguhn, A., Traub, R. D., Schmitz, D. & Jefferys, J. G. Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro. Nature 394, 189-192 (1998).
59. Schmitz, D. et al. Axo-axonal coupling. A novel mechanism for ultrafast neuronal communication. Neuron 31, 831-840 (2001). Reports dye coupling between putative axons of principal cells, as shown by confocal laser scanning micoscropy.
60. Spruston N. Axonal gap junctions send ripples through the hippocampus. Neuron 31, 669-671 (2001).
61. Maier, N., Nimmrich, V. & Draguhn, A. Cellular and network mechanisms underlying spontaneous sharp wave-ripple complexes in mouse hippocampal slices. J. Physiol. (Lond.) 550, 873-887 (2003).
62. Towers, S. K. et al. Fast network oscillations in the rat dentate gyrus in vitro. J. Neurophysiol. 87, 1165-1168 (2002).
63. LeBeau, F. E., Towers, S. K., Traub, R. D., Whittington, M. A. & Buhl, E. H. Fast network oscillations induced by potassium transients in the rat hippocampus in vitro. J. Physiol. (Lond.) 542, 167-179 (2002).
64. Pais, T. et al. Sharp-wave like activity in hippocampus in vitro in mice lacking the gap junction protein connexin 36. J. Neurophysiol. 89, 2046-2054 (2003).
65. Gillies, M. J. et al. A model of atropine-resistant theta oscillations in rat hippocampal area CA1. J. Physiol. (Lond.) 543, 779-793 (2002).
66. Blatow, M. et al. A novel network of muitipolar bursting interneurons generates theta frequency oscillations in neocortex. Neuron 36, 805-817 (2003).
67. Montoro, R. J. & Yuste, R. Gap junctions in developing neocortex: a review. Brain Res. Brain Res. Rev. 47, 216-226 (2004).
68. Galarreta, M. & Hestrin, S. Spike transmission and synchrony detection in networks of GABAergic interneurons. Science 292, 2295-2299 (2001).
69. 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).
70. Belerlein, M., Gibson, J. R. & Connors, B. W. A network of electrically coupled interneurons drives synchronized inhibition in neocortex. Nature Neurosci. 3, 904-910 (2000).
71. Szabadics, J., Lorincz, A. & Tamas, G. Beta and gamma frequency synchronization by dendritic GABAergic synapses and gap junctions in a network of cortical interneurons. J. Neurosci. 21, 5824-5831 (2001).
72. Liu, X. B. & Jones, E. G. Fine structural localization of connexin-36 immunoreactivity in mouse cerebral cortex and thalamus. J. Comp. Neurol. 466, 457-467 (2003).
73. Landisman, C. E. et al. Electrical synapses in the thalamic reticular nucleus. J. Neurosci. 22, 1002-1009 (2002).
74. Long, M. A., Landisman, C. E. & Connors, B. W. Small clusters of electrically coupled neurons generate synchronous rhythms in the thalamic reticular nucleus. J. Neurosci. 24, 341-349 (2004).
75. Usrey, W. M. Spike timing and visual processing in the retinogeniculocortical pathway. Philos. Trans. R. Soc. Lond. B 357, 1729-1737 (2002).
76. Hughes, S. W. et al. Synchronized oscillations at alpha and theta frequencies in the lateral geniculate nucleus. Neuron 42, 253-268 (2004). Showed that high-threshold bursts or burstlets are groups of spikelets with properties of electrotonically transmitted action potentials that are accompanied by dye coupling and abolished by the gap junction blocker CBX.
77. Cook, J. D. & Becker, E. L. Gap junctions in the vertebrate retina. Microsc. Res. Tech. 31, 408-419 (1995).
78. Feigenspan, A., Teubner, B., Willecke, K. & Weiler, R. Expression of neuronal connexin36 in All amacrine cells of the mammalian retina. J. Neurosci. 21, 230-239 (2001).
79. Mills, S. L., O'Brien, J. J., Li, W., O'Brien, J. & Massey S. C. Rod pathways in the mammalian retina use connexin 36. J. Comp. Neurol. 436, 336-350 (2001).
80. Lee, E. J. et al. The immunocytochemical localization of connexin 36 at rod and cone gap junctions in the guinea pig retina. Eur. J. Neurosci. 18, 2925-2934 (2003).
81. Feigenspan, A. et al. Expression of connexin36 in cone pedicles and OFF-cone bipolar cells of the mouse retina. J. Neurosci. 24, 3325-3334 (2004).
82. Hidaka, S., Akahori, Y. & Kurosawa, Y. Dendrodendritic electrical synapses between mammalian retinal ganglion cells. J. Neurosci. 24, 10553-10567 (2004).
83. Deans, M. R., Volgyi, B., Goodenough, D. A., Bloomfield, S. A. & Paul, D. L. Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina. Neuron 36, 703-712 (2002).
84. Schubert, T. et al. Connexin36 mediates coupling of α-ganglion cells in mouse retina. J. Comp. Neurol. (in the press).
85. Deans, M. R. & Paul, D. L. Mouse horizontal cells do not express connexin26 or connexin36. Cell Commun. Adhes. 8, 361-366 (2001).
86. Dang, L. et al. Connexin 36 in photoreceptor cells: studies on transgenic rod-less and cone-less mouse retinas. Mol. Vis. 11, 323-327 (2004).
87. Demb, J. B. & Pugh, E. N. Connexin36 forms synapses essential for night vision. Neuron 36, 551-553 (2002).
88. Massey, S. C. et al. Multiple neuronal connexins in the mammalian retina. Cell Commun. Adhes. 10, 425-430 (2003).
89. DeVries, S. H., Qi, X., Smith, R., Makous, W. & Sterling, P. Electrical coupling between mammalian cones. Curr. Biol. 12, 1900-1907 (2002).
90. Laughlin, S. B. Retinal function: coupling cones clarifies vision. Curr. Biol. 12, R833-R834 (2002).
91. Veruki, M. L. & Hartveit, E. All (rod) amacrine cells form a network of electrically coupled interneurons in the mammalian retina. Neuron 33, 935-946 (2002).
92. Hornstein, E. P., Verweij, J. & Schnapf, J. L. Electrical coupling between red and green cones in primate retina. Nature Neurosci. 7, 745-750 (2004).
93. Li, W. & DeVries, S. H. Separate blue and green cone networks in the mammalian retina. Nature Neurosci. 7, 751-756 (2004).
94. Tsukamoto, Y., Morigiwa, K., Ueda, M. & Sterling, P. Microcircuits for night vision in mouse retina. J. Neurosci. 21, 8616-8623 (2001).
95. Li, W., Keung, J. W. & Massey, S. C. Direct synaptic connections between rods and OFF cone bipolar cells in the rabbi retina. J. Comp. Neurol. 474, 1-12 (2004).
96. Kamermans, M. & Fahrenfort, I. Ephaptic interactions within a chemical synapse: hemichannel-mediated ephaptic inhibition in the retina. Curr. Opin. Neurobiol. 14, 531-541 (2004).
97. He, S., Weiler, R. & Vaney, D. I. Endogenous dopaminergic regulation of horizontal cell coupling in the mammalian retina. J. Comp. Neurol. 418, 33-40 (2000).
98. Janssen-Bienhold, U. et al. Identification and localization of connexin26 within the photoreceptor-horizontal cell synaptic complex. Vis. Neurosci. 18, 169-178 (2001).
99. Kamermans, M. et al. Hemichannel-mediated inhibition in the outer retina. Science 292, 1178-1180 (2001).
100. Pottek, M. et al. Contribution of connexin26 to electrical feedback inhibition in the turtle retina. J. Comp. Neurol. 466, 468-477 (2003).
101. Güldenagel, M. et al. Expression patterns of connexin genes in mouse retina. J. Comp. Neurol. 425, 193-201 (2000).
102. Bloomfield, S. A., Xin, D. & Osborne, T. Light-induced modulation of coupling between All amacrine cells in the rabbit retina. Vis. Neurosci. 14 565-576 (1997).
103. Bloomfield, S. A. & Volgyi, B. Function and plasticity of homologous coupling between All amacrine cells. Vision Res. 44, 3297-3306 (2004).
104. Veruki, M. L. & Hartveit, E. Electrical synapses mediate signal transmission in the rod pathway of the mammalian retina. J. Neurosci. 22, 10558-10566 (2002).
105. Mas, C. et al. Association of the connexin36 gene with juvenile myoclonic epilepsy. J. Med. Genet. 41, e93 (2004).
106. Krüger, O. et al. Defective vascular development in connexin 45-deficient mice. Development 127, 4179-4193 (2000).
107. Srintvas, M. et al. Functional properties of channels formed by the neuronal gap junction protein connexin36. J. Neurosci. 19, 9848-9855 (1999).
108. Moreno, A. P., Laing, J. G., Beyer, E. C. & Spray, D. C. Properties of gap junction channels formed of connexin 45 endogenously expressed in human hepatoma (SKHep1) cells. Am. J. Physiol. 268, C356-C365 (1995).
109. Martinez, A. D., Hayrapetyan, V., Moreno, A. P. & Beyer, E. C. A carboxyl terminal domain of connexin43 is critical for gap junction plaque formation but not for homo- or hetero-oligomerization. Cell Commun. Adhes. 10, 323-328 (2003).