Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology?

Cellular and Molecular Life Sciences

Volumn 72, Issue 15, 2015, Pages 2823-2851

  Decrock, Elke ^a   De Bock, Marijke ^a   Wang, Nan ^a   Bultynck, Geert ^b   Giaume, Christian ^c,d,e   Naus, Christian C ^f   Green, Colin R ^g   Leybaert, Luc ^a  

^a GHENT UNIVERSITY   (Belgium)

^b LABORATORY OF MOLECULAR AND CELLULAR SIGNALING   (Belgium)

^c CNRS   (France)

^d SORBONNE UNIVERSITÉ   (France)

^e PSL RESEARCH UNIVERSITY   (France)

^f UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^g UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

Blood brain barrier; Central nervous system; Connexin; Glia; Neuron; Pannexin; Pathology; Physiology

Indexed keywords

CONNEXIN 30; CONNEXIN 43; GAP JUNCTION PROTEIN; MEMBRANE PROTEIN; PANNEXIN; UNCLASSIFIED DRUG;

ACCURACY; ASTROCYTE; BLOOD BRAIN BARRIER; BRAIN DEVELOPMENT; CENTRAL NERVOUS SYSTEM DISEASE; CENTRAL NERVOUS SYSTEM FUNCTION; DISEASE ACTIVITY; DISEASE ASSOCIATION; ELECTRICAL SYNAPSE; GAP JUNCTION; GLIA CELL; HUMAN; MICROGLIA; MOLECULAR DYNAMICS; MOLECULAR PATHOLOGY; MOTOR CONTROL; NERVE CELL NETWORK; NERVE CELL PLASTICITY; NONHUMAN; PROTEIN DETERMINATION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION; SYNAPTIC TRANSMISSION; ANIMAL; CENTRAL NERVOUS SYSTEM; METABOLISM; NERVOUS SYSTEM FUNCTION; PATHOLOGY; PHYSIOLOGY;

ANIMALS; CENTRAL NERVOUS SYSTEM; CONNEXINS; GAP JUNCTIONS; HUMANS; NERVOUS SYSTEM PHYSIOLOGICAL PHENOMENA; SIGNAL TRANSDUCTION;

EID: 84937732480     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-015-1962-7     Document Type: Review

References (381)

1. Allen NJ, Barres BA (2009) Neuroscience: glia - more than just brain glue. Nature 457(7230):675-677. doi: 10.1038/457675a
2. Min R, Santello M, Nevian T (2012) The computational power of astrocyte mediated synaptic plasticity. Front Comput Neurosci 6:93
3. Ben Achour S, Pascual O (2010) Glia: the many ways to modulate synaptic plasticity. Neurochem Int 57(4):440-445
4. Perea G, Araque A (2010) GLIA modulates synaptic transmission. Brain Res Rev 63(1-2):93-102. doi: 10.1016/j.brainresrev.2009.10.005
5. Ezan P, Andre P, Cisternino S, Saubamea B, Boulay AC, Doutremer S, Thomas MA, Quenech'du N, Giaume C, Cohen-Salmon M (2012) Deletion of astroglial connexins weakens the blood-brain barrier. J Cereb Blood Flow Metab 32(8):1457-1467. doi: 10.1038/jcbfm.2012.45
6. Iadecola C, Nedergaard M (2007) Glial regulation of the cerebral microvasculature. Nat Neurosci 10(11):1369-1376. doi: 10.1038/nn2003
7. Leybaert L (2005) Neurobarrier coupling in the brain: a partner of neurovascular and neurometabolic coupling? J Cereb Blood Flow Metab 25(1):2-16. doi: 10.1038/sj.jcbfm.9600001
8. Santello M, Cali C, Bezzi P (2012) Gliotransmission and the tripartite synapse. Adv Exp Med Biol 970:307-331
9. Neuwelt EA, Bauer B, Fahlke C, Fricker G, Iadecola C, Janigro D, Leybaert L, Molnar Z, O'Donnell ME, Povlishock JT, Saunders NR, Sharp F, Stanimirovic D, Watts RJ, Drewes LR (2011) Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci 12(3):169-182
10. Straub SV, Nelson MT (2007) Astrocytic calcium signaling: the information currency coupling neuronal activity to the cerebral microcirculation. Trends Cardiovasc Med 17(6):183-190. doi: 10.1016/j.tcm.2007.05.001
11. Girouard H, Iadecola C (2006) Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease. J Appl Physiol 100(1):328-335. doi: 10.1152/japplphysiol.00966.2005
12. Pellerin L, Bouzier-Sore AK, Aubert A, Serres S, Merle M, Costalat R, Magistretti PJ (2007) Activity-dependent regulation of energy metabolism by astrocytes: an update. Glia 55(12):1251-1262. doi: 10.1002/glia.20528
13. Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57(2):173-185
14. De Bock M, Decrock E, Wang N, Bol M, Vinken M, Bultynck G, Leybaert L (2014) The dual face of connexin-based astroglial Ca(2+) communication: a key player in brain physiology and a prime target in pathology. Biochim Biophys Acta 1843(10):2211-2232
15. Sohl G, Willecke K (2003) An update on connexin genes and their nomenclature in mouse and man. Cell Commun Adhes 10(4-6):173-180
16. De Bock M, Kerrebrouck M, Wang N, Leybaert L (2013) Neurological manifestations of oculodentodigital dysplasia: a Cx43 channelopathy of the central nervous system? Front Pharmacol 4:120
17. Nagy JI, Rash JE (2000) Connexins and gap junctions of astrocytes and oligodendrocytes in the CNS. Brain Res Brain Res Rev 32(1):29-44
18. Theis M, Giaume C (2012) Connexin-based intercellular communication and astrocyte heterogeneity. Brain Res 1487:88-98
19. Cina C, Bechberger JF, Ozog MA, Naus CC (2007) Expression of connexins in embryonic mouse neocortical development. J Comp Neurol 504(3):298-313
20. Eugenin EA, Basilio D, Saez JC, Orellana JA, Raine CS, Bukauskas F, Bennett MV, Berman JW (2012) The role of gap junction channels during physiologic and pathologic conditions of the human central nervous system. J Neuroimmune Pharmacol 7(3):499-518
21. Lee IH, Lindqvist E, Kiehn O, Widenfalk J, Olson L (2005) Glial and neuronal connexin expression patterns in the rat spinal cord during development and following injury. J Comp Neurol 489(1):1-10
22. Volgyi B, Kovacs-Oller T, Atlasz T, Wilhelm M, Gabriel R (2013) Gap junctional coupling in the vertebrate retina: variations on one theme? Prog Retin Eye Res 34:1-18
23. Vogt A, Hormuzdi SG, Monyer H (2005) Pannexin1 and Pannexin2 expression in the developing and mature rat brain. Brain Res Mol Brain Res 141(1):113-120
24. Cone AC, Ambrosi C, Scemes E, Martone ME, Sosinsky GE (2013) A comparative antibody analysis of pannexin1 expression in four rat brain regions reveals varying subcellular localizations. Front Pharmacol 4:6
25. Penuela S, Gehi R, Laird DW (2013) The biochemistry and function of pannexin channels. Biochim Biophys Acta 1828(1):15-22
26. Litvin O, Tiunova A, Connell-Alberts Y, Panchin Y, Baranova A (2006) What is hidden in the pannexin treasure trove: the sneak peek and the guesswork. J Cell Mol Med 10(3):613-634
27. Ray A, Zoidl G, Weickert S, Wahle P, Dermietzel R (2005) Site-specific and developmental expression of pannexin1 in the mouse nervous system. Eur J Neurosci 21(12):3277-3290
28. Le Vasseur M, Lelowski J, Bechberger JF, Sin WC, Naus CC (2014) Pannexin 2 protein expression is not restricted to the CNS. Front Cell Neurosci 8:392
29. Bravo D, Ibarra P, Retamal J, Pelissier T, Laurido C, Hernandez A, Constandil L (2014) Pannexin 1: a novel participant in neuropathic pain signaling in the rat spinal cord. Pain 155(10):2108-2115
30. Kranz K, Dorgau B, Pottek M, Herrling R, Schultz K, Bolte P, Monyer H, Penuela S, Laird DW, Dedek K, Weiler R, Janssen-Bienhold U (2013) Expression of Pannexin1 in the outer plexiform layer of the mouse retina and physiological impact of its knockout. J Comp Neurol 521(5):1119-1135
31. Harris AL (2007) Connexin channel permeability to cytoplasmic molecules. Prog Biophys Mol Biol 94(1-2):120-143
32. Connors BW, Long MA (2004) Electrical synapses in the mammalian brain. Annu Rev Neurosci 27:393-418
33. Giaume C, Koulakoff A, Roux L, Holcman D, Rouach N (2010) Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat Rev Neurosci 11(2):87-99
34. Pereda AE (2014) Electrical synapses and their functional interactions with chemical synapses. Nat Rev Neurosci 15(4):250-263
35. Wang N, De Bock M, Decrock E, Bol M, Gadicherla A, Vinken M, Rogiers V, Bukauskas FF, Bultynck G, Leybaert L (2013) Paracrine signaling through plasma membrane hemichannels. Biochim Biophys Acta 1828(1):35-50
36. Saez JC, Leybaert L (2014) Hunting for connexin hemichannels. FEBS Lett 588(8):1205-1211
37. Kang J, Kang N, Lovatt D, Torres A, Zhao Z, Lin J, Nedergaard M (2008) Connexin 43 hemichannels are permeable to ATP. J Neurosci 28(18):4702-4711
38. Ye ZC, Wyeth MS, Baltan-Tekkok S, Ransom BR (2003) Functional hemichannels in astrocytes: a novel mechanism of glutamate release. J Neurosci 23(9):3588-3596
39. Burnstock G, Krugel U, Abbracchio MP, Illes P (2011) Purinergic signalling: from normal behaviour to pathological brain function. Prog Neurobiol 95(2):229-274. doi: 10.1016/j.pneurobio.2011.08.006
40. Meldrum BS (2000) Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 130(4S Suppl):1007S-1015S
41. Contreras JE, Saez JC, Bukauskas FF, Bennett MV (2003) Gating and regulation of connexin 43 (Cx43) hemichannels. Proc Natl Acad Sci USA 100(20):11388-11393. doi: 10.1073/pnas.1434298100
42. Gomes P, Srinivas SP, Van Driessche W, Vereecke J, Himpens B (2005) ATP release through connexin hemichannels in corneal endothelial cells. Invest Ophthalmol Vis Sci 46(4):1208-1218
43. De Vuyst E, Decrock E, De Bock M, Yamasaki H, Naus CC, Evans WH, Leybaert L (2007) Connexin hemichannels and gap junction channels are differentially influenced by lipopolysaccharide and basic fibroblast growth factor. Mol Biol Cell 18(1):34-46. doi: 10.1091/mbc.E06-03-0182
44. Contreras JE, Sanchez HA, Eugenin EA, Speidel D, Theis M, Willecke K, Bukauskas FF, Bennett MV, Saez JC (2002) Metabolic inhibition induces opening of unopposed connexin 43 gap junction hemichannels and reduces gap junctional communication in cortical astrocytes in culture. Proc Natl Acad Sci USA 99(1):495-500
45. Retamal MA, Froger N, Palacios-Prado N, Ezan P, Saez PJ, Saez JC, Giaume C (2007) Cx43 hemichannels and gap junction channels in astrocytes are regulated oppositely by proinflammatory cytokines released from activated microglia. J Neurosci 27(50):13781-13792. doi: 10.1523/JNEUROSCI.2042-07.2007
46. Ramachandran S, Xie LH, John SA, Subramaniam S, Lal R (2007) A novel role for connexin hemichannel in oxidative stress and smoking-induced cell injury. PLoS One 2(8):e712
47. De Vuyst E, Wang N, Decrock E, De Bock M, Vinken M, Van Moorhem M, Lai C, Culot M, Rogiers V, Cecchelli R, Naus CC, Evans WH, Leybaert L (2009) Ca(2+) regulation of connexin 43 hemichannels in C6 glioma and glial cells. Cell Calcium 46(3):176-187. doi: 10.1016/j.ceca.2009.07.002
48. Thimm J, Mechler A, Lin H, Rhee S, Lal R (2005) Calcium-dependent open/closed conformations and interfacial energy maps of reconstituted hemichannels. J Biol Chem 280(11):10646-10654
49. De Vuyst E, Decrock E, Cabooter L, Dubyak GR, Naus CC, Evans WH, Leybaert L (2006) Intracellular calcium changes trigger connexin 32 hemichannel opening. EMBO J 25(1):34-44. doi: 10.1038/sj.emboj.7600908
50. i responses. Mol Biol Cell 19(8):3501-3513. doi: 10.1091/mbc.E07-12-1240
51. Belliveau DJ, Bani-Yaghoub M, McGirr B, Naus CC, Rushlow WJ (2006) Enhanced neurite outgrowth in PC12 cells mediated by connexin hemichannels and ATP. J Biol Chem 281(30):20920-20931. doi: 10.1074/jbc.M600026200
52. Orellana JA, Froger N, Ezan P, Jiang JX, Bennett MV, Naus CC, Giaume C, Saez JC (2011) ATP and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels. J Neurochem 118(5):826-840. doi: 10.1111/j.1471-4159.2011.07210.x
53. 2+ in transfected HeLa cells. Am J Physiol Cell Physiol 297(3):C665-C678
54. i in rabbit ventricular myocytes during metabolic inhibition. J Mol Cell Cardiol 33(12):2145-2155
55. Baranova A, Ivanov D, Petrash N, Pestova A, Skoblov M, Kelmanson I, Shagin D, Nazarenko S, Geraymovych E, Litvin O, Tiunova A, Born TL, Usman N, Staroverov D, Lukyanov S, Panchin Y (2004) The mammalian pannexin family is homologous to the invertebrate innexin gap junction proteins. Genomics 83(4):706-716
56. Iwabuchi S, Kawahara K (2011) Functional significance of the negative-feedback regulation of ATP release via pannexin-1 hemichannels under ischemic stress in astrocytes. Neurochem Int 58(3):376-384
57. Orellana JA, Shoji KF, Abudara V, Ezan P, Amigou E, Saez PJ, Jiang JX, Naus CC, Saez JC, Giaume C (2011) Amyloid beta-induced death in neurons involves glial and neuronal hemichannels. J Neurosci 31(13):4962-4977. doi: 10.1523/JNEUROSCI.6417-10.2011
58. Suadicani SO, Iglesias R, Wang J, Dahl G, Spray DC, Scemes E (2012) ATP signaling is deficient in cultured Pannexin1-null mouse astrocytes. Glia 60(7):1106-1116
59. MacVicar BA, Thompson RJ (2010) Non-junction functions of pannexin-1 channels. Trends Neurosci 33(2):93-102
60. Ambrosi C, Gassmann O, Pranskevich JN, Boassa D, Smock A, Wang J, Dahl G, Steinem C, Sosinsky GE (2010) Pannexin1 and Pannexin2 channels show quaternary similarities to connexons and different oligomerization numbers from each other. J Biol Chem 285(32):24420-24431
61. Wicki-Stordeur LE, Boyce AK, Swayne LA (2013) Analysis of a pannexin 2-pannexin 1 chimeric protein supports divergent roles for pannexin C-termini in cellular localization. Cell Commun Adhes 20(3-4):73-79
62. Swayne LA, Sorbara CD, Bennett SA (2010) Pannexin 2 is expressed by postnatal hippocampal neural progenitors and modulates neuronal commitment. J Biol Chem 285(32):24977-24986
63. Penuela S, Bhalla R, Nag K, Laird DW (2009) Glycosylation regulates pannexin intermixing and cellular localization. Mol Biol Cell 20(20):4313-4323
64. Sosinsky GE, Boassa D, Dermietzel R, Duffy HS, Laird DW, MacVicar B, Naus CC, Penuela S, Scemes E, Spray DC, Thompson RJ, Zhao HB, Dahl G (2011) Pannexin channels are not gap junction hemichannels. Channels (Austin) 5(3):193-197
65. Dahl G, Muller KJ (2014) Innexin and pannexin channels and their signaling. FEBS Lett 588(8):1396-1402
66. Thompson RJ, Zhou N, MacVicar BA (2006) Ischemia opens neuronal gap junction hemichannels. Science 312(5775):924-927
67. Orellana JA, Montero TD, von Bernhardi R (2013) Astrocytes inhibit nitric oxide-dependent Ca(2+) dynamics in activated microglia: involvement of ATP released via pannexin 1 channels. Glia 61(12):2023-2037
68. Iglesias R, Dahl G, Qiu F, Spray DC, Scemes E (2009) Pannexin 1: the molecular substrate of astrocyte "hemichannels". J Neurosci 29(21):7092-7097
69. Huang Y, Grinspan JB, Abrams CK, Scherer SS (2007) Pannexin1 is expressed by neurons and glia but does not form functional gap junctions. Glia 55(1):46-56
70. Wei H, Deng F, Chen Y, Qin Y, Hao Y, Guo X (2014) Ultrafine carbon black induces glutamate and ATP release by activating connexin and pannexin hemichannels in cultured astrocytes. Toxicology 323:32-41
71. Santiago MF, Veliskova J, Patel NK, Lutz SE, Caille D, Charollais A, Meda P, Scemes E (2011) Targeting pannexin1 improves seizure outcome. PLoS One 6(9):e25178
72. Bao L, Locovei S, Dahl G (2004) Pannexin membrane channels are mechanosensitive conduits for ATP. FEBS Lett 572(1-3):65-68
73. Weilinger NL, Tang PL, Thompson RJ (2012) Anoxia-induced NMDA receptor activation opens pannexin channels via Src family kinases. J Neurosci 32(36):12579-12588
74. Sridharan M, Adderley SP, Bowles EA, Egan TM, Stephenson AH, Ellsworth ML, Sprague RS (2010) Pannexin 1 is the conduit for low oxygen tension-induced ATP release from human erythrocytes. Am J Physiol Heart Circ Physiol 299(4):H1146-H1152
75. Locovei S, Wang J, Dahl G (2006) Activation of pannexin 1 channels by ATP through P2Y receptors and by cytoplasmic calcium. FEBS Lett 580(1):239-244
76. Ma W, Hui H, Pelegrin P, Surprenant A (2009) Pharmacological characterization of pannexin-1 currents expressed in mammalian cells. J Pharmacol Exp Ther 328(2):409-418
77. Sandilos JK, Chiu YH, Chekeni FB, Armstrong AJ, Walk SF, Ravichandran KS, Bayliss DA (2012) Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore-associated C-terminal autoinhibitory region. J Biol Chem 287(14):11303-11311
78. Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25(21):5071-5082
79. Locovei S, Scemes E, Qiu F, Spray DC, Dahl G (2007) Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex. FEBS Lett 581(3):483-488
80. Thompson RJ, Jackson MF, Olah ME, Rungta RL, Hines DJ, Beazely MA, MacDonald JF, MacVicar BA (2008) Activation of pannexin-1 hemichannels augments aberrant bursting in the hippocampus. Science 322(5907):1555-1559
81. Bruzzone R, Hormuzdi SG, Barbe MT, Herb A, Monyer H (2003) Pannexins, a family of gap junction proteins expressed in brain. Proc Natl Acad Sci USA 100(23):13644-13649
82. Bodendiek SB, Raman G (2010) Connexin modulators and their potential targets under the magnifying glass. Curr Med Chem 17(34):4191-4230
83. D'Hondt C, Ponsaerts R, De Smedt H, Bultynck G, Himpens B (2009) Pannexins, distant relatives of the connexin family with specific cellular functions? Bioessays 31(9):953-974
84. Iyyathurai J, D'Hondt C, Wang N, De Bock M, Himpens B, Retamal MA, Stehberg J, Leybaert L, Bultynck G (2013) Peptides and peptide-derived molecules targeting the intracellular domains of Cx43: Gap junctions versus hemichannels. Neuropharmacology 75:491-505
85. Wang N, De Bock M, Decrock E, Bol M, Gadicherla A, Bultynck G, Leybaert L (2013) Connexin targeting peptides as inhibitors of voltage- and intracellular Ca-triggered Cx43 hemichannel opening. Neuropharmacology 75:506-516
86. Evans WH, Bultynck G, Leybaert L (2012) Manipulating connexin communication channels: use of peptidomimetics and the translational outputs. J Membr Biol 245(8):437-449
87. 2+ elevation. Basic Res Cardiol 107(6):304
88. O'Carroll SJ, Alkadhi M, Nicholson LF, Green CR (2008) Connexin 43 mimetic peptides reduce swelling, astrogliosis, and neuronal cell death after spinal cord injury. Cell Commun Adhes 15(1):27-42
89. De Bock M, Culot M, Wang N, Bol M, Decrock E, De Vuyst E, da Costa A, Dauwe I, Vinken M, Simon AM, Rogiers V, De Ley G, Evans WH, Bultynck G, Dupont G, Cecchelli R, Leybaert L (2011) Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood-brain barrier permeability. J Cereb Blood Flow Metab 31(9):1942-1957
90. Decrock E, De Vuyst E, Vinken M, Van Moorhem M, Vranckx K, Wang N, Van Laeken L, De Bock M, D'Herde K, Lai CP, Rogiers V, Evans WH, Naus CC, Leybaert L (2009) Connexin 43 hemichannels contribute to the propagation of apoptotic cell death in a rat C6 glioma cell model. Cell Death Differ 16(1):151-163. doi: 10.1038/cdd.2008.138
91. Ponsaerts R, De Vuyst E, Retamal M, D'Hondt C, Vermeire D, Wang N, De Smedt H, Zimmermann P, Himpens B, Vereecke J, Leybaert L, Bultynck G (2010) Intramolecular loop/tail interactions are essential for connexin 43-hemichannel activity. Faseb J 24(11):4378-4395
92. Wang N, De Vuyst E, Ponsaerts R, Boengler K, Palacios-Prado N, Wauman J, Lai CP, De Bock M, Decrock E, Bol M, Vinken M, Rogiers V, Tavernier J, Evans WH, Naus CC, Bukauskas FF, Sipido KR, Heusch G, Schulz R, Bultynck G, Leybaert L (2012) Selective inhibition of Cx43 hemichannels by Gap19 and its impact on myocardial ischemia/reperfusion injury. Basic Res Cardiol 108(1):309
93. Elias LA, Wang DD, Kriegstein AR (2007) Gap junction adhesion is necessary for radial migration in the neocortex. Nature 448(7156):901-907. doi: 10.1038/nature06063
94. Olk S, Zoidl G, Dermietzel R (2009) Connexins, cell motility, and the cytoskeleton. Cell Motil Cytoskeleton 66(11):1000-1016
95. Matsuuchi L, Naus CC (2013) Gap junction proteins on the move: connexins, the cytoskeleton and migration. Biochim Biophys Acta 1828(1):94-108
96. Wicki-Stordeur LE, Swayne LA (2014) The emerging Pannexin 1 signalome: a new nexus revealed? Front Cell Neurosci 7:287
97. Vinken M, Decrock E, Leybaert L, Bultynck G, Himpens B, Vanhaecke T, Rogiers V (2012) Non-channel functions of connexins in cell growth and cell death. Biochim Biophys Acta 1818(8):2002-2008
98. Danesh-Meyer HV, Kerr NM, Zhang J, Eady EK, O'Carroll SJ, Nicholson LF, Johnson CS, Green CR (2012) Connexin-43 mimetic peptide reduces vascular leak and retinal ganglion cell death following retinal ischaemia. Brain 135(Pt 2):506-520
99. Davidson JO, Green CR, Bennet L, Nicholson LF, Danesh-Meyer H, O'Carroll SJ, Gunn AJ (2013) A key role for connexin hemichannels in spreading ischemic brain injury. Curr Drug Targets 14(1):36-46
100. Davidson JO, Drury PP, Green CR, Nicholson LF, Bennet L, Gunn AJ (2014) Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep. PLoS One 9(5):e96558
101. Mallard C, Davidson JO, Tan S, Green CR, Bennet L, Robertson NJ, Gunn AJ (2014) Astrocytes and microglia in acute cerebral injury underlying cerebral palsy associated with preterm birth. Pediatr Res 75(1-2):234-240
102. Peinado A, Yuste R, Katz LC (1993) Gap junctional communication and the development of local circuits in neocortex. Cereb Cortex 3(5):488-498
103. Hamzei-Sichani F, Davidson KG, Yasumura T, Janssen WG, Wearne SL, Hof PR, Traub RD, Gutierrez R, Ottersen OP, Rash JE (2012) Mixed electrical-chemical synapses in adult rat hippocampus are primarily glutamatergic and coupled by connexin-36. Front Neuroanat 6:13
104. Belousov AB, Fontes JD (2013) Neuronal gap junctions: making and breaking connections during development and injury. Trends Neurosci 36(4):227-236
105. Meyer AH, Katona I, Blatow M, Rozov A, Monyer H (2002) In vivo labeling of parvalbumin-positive interneurons and analysis of electrical coupling in identified neurons. J Neurosci 22(16):7055-7064
106. Alvarez-Maubecin V, Garcia-Hernandez F, Williams JT, Van Bockstaele EJ (2000) Functional coupling between neurons and glia. J Neurosci 20(11):4091-4098
107. Pakhotin P, Verkhratsky A (2005) Electrical synapses between Bergmann glial cells and Purkinje neurones in rat cerebellar slices. Mol Cell Neurosci 28(1):79-84
108. Traub RD, Kopell N, Bibbig A, Buhl EH, LeBeau FE, Whittington MA (2001) Gap junctions between interneuron dendrites can enhance synchrony of gamma oscillations in distributed networks. J Neurosci 21(23):9478-9486
109. Lee SC, Patrick SL, Richardson KA, Connors BW (2014) Two functionally distinct networks of gap junction-coupled inhibitory neurons in the thalamic reticular nucleus. J Neurosci 34(39):13170-13182
110. Bautista W, Nagy JI, Dai Y, McCrea DA (2012) Requirement of neuronal connexin-36 in pathways mediating presynaptic inhibition of primary afferents in functionally mature mouse spinal cord. J Physiol 590(Pt 16):3821-3839
111. Rash JE, Dillman RK, Bilhartz BL, Duffy HS, Whalen LR, Yasumura T (1996) Mixed synapses discovered and mapped throughout mammalian spinal cord. Proc Natl Acad Sci USA 93(9):4235-4239
112. Condorelli DF, Belluardo N, Trovato-Salinaro A, Mudo G (2000) Expression of Cx36 in mammalian neurons. Brain Res Brain Res Rev 32(1):72-85
113. Rash JE, Staines WA, Yasumura T, Patel D, Furman CS, Stelmack GL, Nagy JI (2000) Immunogold evidence that neuronal gap junctions in adult rat brain and spinal cord contain connexin-36 but not connexin-32 or connexin-43. Proc Natl Acad Sci USA 97(13):7573-7578
114. Gajda Z, Szupera Z, Blazso G, Szente M (2005) Quinine, a blocker of neuronal cx36 channels, suppresses seizure activity in rat neocortex in vivo. Epilepsia 46(10):1581-1591
115. Medina-Ceja L, Ventura-Mejia C (2010) Differential effects of trimethylamine and quinine on seizures induced by 4-aminopyridine administration in the entorhinal cortex of vigilant rats. Seizure 19(8):507-513
116. Bostanci MO, Bagirici F (2007) Anticonvulsive effects of quinine on penicillin-induced epileptiform activity: an in vivo study. Seizure 16(2):166-172
117. Carlen PL (2012) Curious and contradictory roles of glial connexins and pannexins in epilepsy. Brain Res 1487:54-60
118. Jacobson GM, Voss LJ, Melin SM, Mason JP, Cursons RT, Steyn-Ross DA, Steyn-Ross ML, Sleigh JW (2010) Connexin-36 knockout mice display increased sensitivity to pentylenetetrazol-induced seizure-like behaviors. Brain Res 1360:198-204
119. Arumugam H, Liu X, Colombo PJ, Corriveau RA, Belousov AB (2005) NMDA receptors regulate developmental gap junction uncoupling via CREB signaling. Nat Neurosci 8(12):1720-1726
120. Hatton GI (1998) Synaptic modulation of neuronal coupling. Cell Biol Int 22(11-12):765-780
121. Park WM, Wang Y, Park S, Denisova JV, Fontes JD, Belousov AB (2011) Interplay of chemical neurotransmitters regulates developmental increase in electrical synapses. J Neurosci 31(16):5909-5920
122. de Rivero Vaccari JC, Corriveau RA, Belousov AB (2007) Gap junctions are required for NMDA receptor dependent cell death in developing neurons. J Neurophysiol 98(5):2878-2886
123. Pereda AE, Faber DS (1996) Activity-dependent short-term enhancement of intercellular coupling. J Neurosci 16(3):983-992
124. Frantseva MV, Kokarovtseva L, Perez Velazquez JL (2002) Ischemia-induced brain damage depends on specific gap-junctional coupling. J Cereb Blood Flow Metab 22(4):453-462
125. de Pina-Benabou MH, Szostak V, Kyrozis A, Rempe D, Uziel D, Urban-Maldonado M, Benabou S, Spray DC, Federoff HJ, Stanton PK, Rozental R (2005) Blockade of gap junctions in vivo provides neuroprotection after perinatal global ischemia. Stroke 36(10):2232-2237. doi: 10.1161/01.STR.0000182239.75969.d8
126. Beheshti S, Sayyah M, Golkar M, Sepehri H, Babaie J, Vaziri B (2010) Changes in hippocampal connexin 36 mRNA and protein levels during epileptogenesis in the kindling model of epilepsy. Prog Neuropsychopharmacol Biol Psychiatry 34(3):510-515
127. Wang Y, Song JH, Denisova JV, Park WM, Fontes JD, Belousov AB (2012) Neuronal gap junction coupling is regulated by glutamate and plays critical role in cell death during neuronal injury. J Neurosci 32(2):713-725
128. Chang Q, Balice-Gordon RJ (2000) Gap junctional communication among developing and injured motor neurons. Brain Res Brain Res Rev 32(1):242-249
129. Belousov AB, Fontes JD (2014) Neuronal gap junction coupling as the primary determinant of the extent of glutamate-mediated excitotoxicity. J Neural Transm 121(8):837-846
130. Striedinger K, Petrasch-Parwez E, Zoidl G, Napirei M, Meier C, Eysel UT, Dermietzel R (2005) Loss of connexin-36 increases retinal cell vulnerability to secondary cell loss. Eur J Neurosci 22(3):605-616
131. Oguro K, Jover T, Tanaka H, Lin Y, Kojima T, Oguro N, Grooms SY, Bennett MV, Zukin RS (2001) Global ischemia-induced increases in the gap junctional proteins connexin 32 (Cx32) and Cx36 in hippocampus and enhanced vulnerability of Cx32 knock-out mice. J Neurosci 21(19):7534-7542
132. Wang Y, Denisova JV, Kang KS, Fontes JD, Zhu BT, Belousov AB (2010) Neuronal gap junctions are required for NMDA receptor-mediated excitotoxicity: implications in ischemic stroke. J Neurophysiol 104(6):3551-3556
133. Kilb W, Kirischuk S, Luhmann HJ (2011) Electrical activity patterns and the functional maturation of the neocortex. Eur J Neurosci 34(10):1677-1686
134. Noctor SC, Flint AC, Weissman TA, Wong WS, Clinton BK, Kriegstein AR (2002) Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia. J Neurosci 22(8):3161-3173
135. Moore AR, Zhou WL, Sirois CL, Belinsky GS, Zecevic N, Antic SD (2014) Connexin hemichannels contribute to spontaneous electrical activity in the human fetal cortex. Proc Natl Acad Sci USA 111(37):E3919-E3928
136. Hoerder-Suabedissen A, Molnar Z (2015) Development, evolution and pathology of neocortical subplate neurons. Nat Rev Neurosci 16(3):133-146
137. Moore AR, Zhou WL, Jakovcevski I, Zecevic N, Antic SD (2011) Spontaneous electrical activity in the human fetal cortex in vitro. J Neurosci 31(7):2391-2398
138. Singh M, Antik S (2015) Mechanisms of spontaneous electrical activity in the developing cerebral cortex - subplate zone. Faseb J 29(1 Supplement):657-665
139. Schock SC, Leblanc D, Hakim AM, Thompson CS (2008) ATP release by way of connexin 36 hemichannels mediates ischemic tolerance in vitro. Biochem Biophys Res Commun 368(1):138-144
140. Zoidl G, Petrasch-Parwez E, Ray A, Meier C, Bunse S, Habbes HW, Dahl G, Dermietzel R (2007) Localization of the pannexin1 protein at postsynaptic sites in the cerebral cortex and hippocampus. Neuroscience 146(1):9-16
141. Bargiotas P, Krenz A, Monyer H, Schwaninger M (2012) Functional outcome of pannexin-deficient mice after cerebral ischemia. Channels (Austin) 6(6):453-456
142. Thompson RJ (2014) Pannexin channels and ischaemia. J Physiol. doi: 10.1113/jphysiol.2014.282426
143. Zhang L, Deng T, Sun Y, Liu K, Yang Y, Zheng X (2008) Role for nitric oxide in permeability of hippocampal neuronal hemichannels during oxygen glucose deprivation. J Neurosci Res 86(10):2281-2291
144. Mylvaganam S, Zhang L, Wu C, Zhang ZJ, Samoilova M, Eubanks J, Carlen PL, Poulter MO (2010) Hippocampal seizures alter the expression of the pannexin and connexin transcriptome. J Neurochem 112(1):92-102
145. Jiang T, Long H, Ma Y, Long L, Li Y, Li F, Zhou P, Yuan C, Xiao B (2013) Altered expression of pannexin proteins in patients with temporal lobe epilepsy. Mol Med Rep 8(6):1801-1806
146. Silverman WR, de Rivero Vaccari JP, Locovei S, Qiu F, Carlsson SK, Scemes E, Keane RW, Dahl G (2009) The pannexin 1 channel activates the inflammasome in neurons and astrocytes. J Biol Chem 284(27):18143-18151
147. Kawamura M Jr, Ruskin DN, Geiger JD, Boison D, Masino SA (2014) Ketogenic diet sensitizes glucose control of hippocampal excitability. J Lipid Res 55(11):2254-2260
148. Nabavi S, Fox R, Proulx CD, Lin JY, Tsien RY, Malinow R (2014) Engineering a memory with LTD and LTP. Nature 511(7509):348-352
149. Escobar ML, Derrick B (2007) Long-term potentiation and depression as putative mechanisms for memory formation. In: Bermúdez-Rattoni F (ed) Neural Plasticity and Memory: From Genes to Brain Imaging, chap. 2. CRC press, Boca Raton
150. Frisch C, De Souza-Silva MA, Sohl G, Guldenagel M, Willecke K, Huston JP, Dere E (2005) Stimulus complexity dependent memory impairment and changes in motor performance after deletion of the neuronal gap junction protein connexin-36 in mice. Behav Brain Res 157(1):177-185
151. Buhl DL, Harris KD, Hormuzdi SG, Monyer H, Buzsaki G (2003) Selective impairment of hippocampal gamma oscillations in connexin-36 knock-out mouse in vivo. J Neurosci 23(3):1013-1018
152. Allen K, Fuchs EC, Jaschonek H, Bannerman DM, Monyer H (2011) Gap junctions between interneurons are required for normal spatial coding in the hippocampus and short-term spatial memory. J Neurosci 31(17):6542-6552
153. Maier N, Guldenagel M, Sohl G, Siegmund H, Willecke K, Draguhn A (2002) Reduction of high-frequency network oscillations (ripples) and pathological network discharges in hippocampal slices from connexin 36-deficient mice. J Physiol 541(Pt 2):521-528
154. Wang Y, Belousov AB (2011) Deletion of neuronal gap junction protein connexin 36 impairs hippocampal LTP. Neurosci Lett 502(1):30-32
155. Prochnow N, Abdulazim A, Kurtenbach S, Wildforster V, Dvoriantchikova G, Hanske J, Petrasch-Parwez E, Shestopalov VI, Dermietzel R, Manahan-Vaughan D, Zoidl G (2012) Pannexin1 stabilizes synaptic plasticity and is needed for learning. PLoS One 7(12):e51767
156. Ardiles AO, Flores-Munoz C, Toro-Ayala G, Cardenas AM, Palacios AG, Munoz P, Fuenzalida M, Saez JC, Martinez AD (2014) Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice. Front Cell Neurosci 8:326
157. Foster TC (1999) Involvement of hippocampal synaptic plasticity in age-related memory decline. Brain Res Brain Res Rev 30(3):236-249
158. Klaassen LJ, Sun Z, Steijaert MN, Bolte P, Fahrenfort I, Sjoerdsma T, Klooster J, Claassen Y, Shields CR, Ten Eikelder HM, Janssen-Bienhold U, Zoidl G, McMahon DG, Kamermans M (2011) Synaptic transmission from horizontal cells to cones is impaired by loss of connexin hemichannels. PLoS Biol 9(7):e1001107
159. Klaassen LJ, Fahrenfort I, Kamermans M (2012) Connexin hemichannel mediated ephaptic inhibition in the retina. Brain Res 1487:25-38
160. Vroman R, Klaassen LJ, Howlett MH, Cenedese V, Klooster J, Sjoerdsma T, Kamermans M (2014) Extracellular ATP hydrolysis inhibits synaptic transmission by increasing ph buffering in the synaptic cleft. PLoS Biol 12(5):e1001864
161. Kamermans M, Fahrenfort I (2004) Ephaptic interactions within a chemical synapse: hemichannel-mediated ephaptic inhibition in the retina. Curr Opin Neurobiol 14(5):531-541
162. Fahrenfort I, Steijaert M, Sjoerdsma T, Vickers E, Ripps H, van Asselt J, Endeman D, Klooster J, Numan R, ten Eikelder H, von Gersdorff H, Kamermans M (2009) Hemichannel-mediated and pH-based feedback from horizontal cells to cones in the vertebrate retina. PLoS One 4(6):e6090
163. Kemmler R, Schultz K, Dedek K, Euler T, Schubert T (2014) Differential regulation of cone calcium signals by different horizontal cell feedback mechanisms in the mouse retina. J Neurosci 34(35):11826-11843
164. Cina C, Maass K, Theis M, Willecke K, Bechberger JF, Naus CC (2009) Involvement of the cytoplasmic C-terminal domain of connexin-43 in neuronal migration. J Neurosci 29(7):2009-2021
165. Fushiki S, Perez Velazquez JL, Zhang L, Bechberger JF, Carlen PL, Naus CC (2003) Changes in neuronal migration in neocortex of connexin-43 null mutant mice. J Neuropathol Exp Neurol 62(3):304-314
166. Santiago MF, Alcami P, Striedinger KM, Spray DC, Scemes E (2010) The carboxyl-terminal domain of connexin-43 is a negative modulator of neuronal differentiation. J Biol Chem 285(16):11836-11845
167. Qi GJ, Chen Q, Chen LJ, Shu Y, Bu LL, Shao XY, Zhang P, Jiao FJ, Shi J, Tian B (2015) Phosphorylation of connexin 43 by Cdk5 modulates neuronal migration during embryonic brain development. Mol Neurobiol. doi: 10.1007/s12035-015-9190-6
168. Bani-Yaghoub M, Bechberger JF, Naus CC (1997) Reduction of connexin-43 expression and dye-coupling during neuronal differentiation of human NTera2/clone D1 cells. J Neurosci Res 49(1):19-31
169. Kandler K, Katz LC (1995) Neuronal coupling and uncoupling in the developing nervous system. Curr Opin Neurobiol 5(1):98-105
170. Lo Turco JJ, Kriegstein AR (1991) Clusters of coupled neuroblasts in embryonic neocortex. Science 252(5005):563-566
171. Rozental R, Morales M, Mehler MF, Urban M, Kremer M, Dermietzel R, Kessler JA, Spray DC (1998) Changes in the properties of gap junctions during neuronal differentiation of hippocampal progenitor cells. J Neurosci 18(5):1753-1762
172. Duval N, Gomes D, Calaora V, Calabrese A, Meda P, Bruzzone R (2002) Cell coupling and Cx43 expression in embryonic mouse neural progenitor cells. J Cell Sci 115(Pt 16):3241-3251
173. Iacobas DA, Iacobas S, Spray DC (2007) Connexin-dependent transcellular transcriptomic networks in mouse brain. Prog Biophys Mol Biol 94(1-2):169-185. doi: 10.1016/j.pbiomolbio.2007.03.015
174. Scemes E, Duval N, Meda P (2003) Reduced expression of P2Y1 receptors in connexin-43-null mice alters calcium signaling and migration of neural progenitor cells. J Neurosci 23(36):11444-11452
175. Rinaldi F, Hartfield EM, Crompton LA, Badger JL, Glover CP, Kelly CM, Rosser AE, Uney JB, Caldwell MA (2014) Cross-regulation of Connexin-43 and beta-catenin influences differentiation of human neural progenitor cells. Cell Death Dis 5:e1017
176. Hartfield EM, Rinaldi F, Glover CP, Wong LF, Caldwell MA, Uney JB (2011) Connexin 36 expression regulates neuronal differentiation from neural progenitor cells. PLoS One 6(3):e14746
177. Weissman TA, Riquelme PA, Ivic L, Flint AC, Kriegstein AR (2004) Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43(5):647-661. doi: 10.1016/j.neuron.2004.08.015
178. Pearson RA, Luneborg NL, Becker DL, Mobbs P (2005) Gap junctions modulate interkinetic nuclear movement in retinal progenitor cells. J Neurosci 25(46):10803-10814
179. Elias LA, Turmaine M, Parnavelas JG, Kriegstein AR (2010) Connexin 43 mediates the tangential to radial migratory switch in ventrally derived cortical interneurons. J Neurosci 30(20):7072-7077
180. Kunze A, Congreso MR, Hartmann C, Wallraff-Beck A, Huttmann K, Bedner P, Requardt R, Seifert G, Redecker C, Willecke K, Hofmann A, Pfeifer A, Theis M, Steinhauser C (2009) Connexin expression by radial glia-like cells is required for neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA 106(27):11336-11341
181. Liebmann M, Stahr A, Guenther M, Witte OW, Frahm C (2013) Astrocytic Cx43 and Cx30 differentially modulate adult neurogenesis in mice. Neurosci Lett 545:40-45
182. Marins M, Xavier AL, Viana NB, Fortes FS, Froes MM, Menezes JR (2009) Gap junctions are involved in cell migration in the early postnatal subventricular zone. Dev Neurobiol 69(11):715-730
183. Freitas AS, Xavier AL, Furtado CM, Hedin-Pereira C, Froes MM, Menezes JR (2012) Dye coupling and connexin expression by cortical radial glia in the early postnatal subventricular zone. Dev Neurobiol 72(12):1482-1497
184. Khodosevich K, Zuccotti A, Kreuzberg MM, Le Magueresse C, Frank M, Willecke K, Monyer H (2012) Connexin-45 modulates the proliferation of transit-amplifying precursor cells in the mouse subventricular zone. Proc Natl Acad Sci USA 109(49):20107-20112
185. Wicki-Stordeur LE, Dzugalo AD, Swansburg RM, Suits JM, Swayne LA (2012) Pannexin 1 regulates postnatal neural stem and progenitor cell proliferation. Neural Dev 7:11
186. Wicki-Stordeur LE, Swayne LA (2013) Panx1 regulates neural stem and progenitor cell behaviours associated with cytoskeletal dynamics and interacts with multiple cytoskeletal elements. Cell Commun Signal 11:62
187. Bhalla-Gehi R, Penuela S, Churko JM, Shao Q, Laird DW (2010) Pannexin1 and pannexin3 delivery, cell surface dynamics, and cytoskeletal interactions. J Biol Chem 285(12):9147-9160
188. Winner B, Winkler J (2015) Adult neurogenesis in neurodegenerative diseases. Cold Spring Harb Perspect Biol 7(4):a021287
189. Jun H, Mohammed Qasim Hussaini S, Rigby MJ, Jang MH (2012) Functional role of adult hippocampal neurogenesis as a therapeutic strategy for mental disorders. Neural Plast 2012:854285
190. Dallerac G, Chever O, Rouach N (2013) How do astrocytes shape synaptic transmission? Insights from electrophysiology. Front Cell Neurosci 7:159
191. Dermietzel R, Hertberg EL, Kessler JA, Spray DC (1991) Gap junctions between cultured astrocytes: immunocytochemical, molecular, and electrophysiological analysis. J Neurosci 11(5):1421-1432
192. Rouach N, Koulakoff A, Abudara V, Willecke K, Giaume C (2008) Astroglial metabolic networks sustain hippocampal synaptic transmission. Science 322(5907):1551-1555. doi: 10.1126/science.1164022
193. Simard M, Arcuino G, Takano T, Liu QS, Nedergaard M (2003) Signaling at the gliovascular interface. J Neurosci 23(27):9254-9262
194. Koulakoff A, Ezan P, Giaume C (2008) Neurons control the expression of connexin 30 and connexin 43 in mouse cortical astrocytes. Glia 56(12):1299-1311. doi: 10.1002/glia.20698
195. Wallraff A, Kohling R, Heinemann U, Theis M, Willecke K, Steinhauser C (2006) The impact of astrocytic gap junctional coupling on potassium buffering in the hippocampus. J Neurosci 26(20):5438-5447. doi: 10.1523/JNEUROSCI.0037-06.2006
196. Nagy JI, Lynn BD, Tress O, Willecke K, Rash JE (2011) Connexin-26 expression in brain parenchymal cells demonstrated by targeted connexin ablation in transgenic mice. Eur J Neurosci 34(2):263-271. doi: 10.1111/j.1460-9568.2011.07741.x
197. Dermietzel R, Gao Y, Scemes E, Vieira D, Urban M, Kremer M, Bennett MV, Spray DC (2000) Connexin-43 null mice reveal that astrocytes express multiple connexins. Brain Res Brain Res Rev 32(1):45-56
198. Scemes E, Dermietzel R, Spray DC (1998) Calcium waves between astrocytes from Cx43 knockout mice. Glia 24(1):65-73
199. Nagy JI, Patel D, Ochalski PA, Stelmack GL (1999) Connexin-30 in rodent, cat and human brain: selective expression in gray matter astrocytes, co-localization with connexin-43 at gap junctions and late developmental appearance. Neuroscience 88(2):447-468
200. Pannasch U, Vargova L, Reingruber J, Ezan P, Holcman D, Giaume C, Sykova E, Rouach N (2011) Astroglial networks scale synaptic activity and plasticity. Proc Natl Acad Sci USA 108(20):8467-8472
201. Lutz SE, Zhao Y, Gulinello M, Lee SC, Raine CS, Brosnan CF (2009) Deletion of astrocyte connexins 43 and 30 leads to a dysmyelinating phenotype and hippocampal CA1 vacuolation. J Neurosci 29(24):7743-7752
202. Giaume C (2010) Astroglial wiring is adding complexity to neuroglial networking. Front Neuroenergetics. doi: 10.3389/fnene.2010.00129
203. Newman EA (2001) Propagation of intercellular calcium waves in retinal astrocytes and Muller cells. J Neurosci 21(7):2215-2223
204. Scemes E, Suadicani SO, Spray DC (2000) Intercellular communication in spinal cord astrocytes: fine tuning between gap junctions and P2 nucleotide receptors in calcium wave propagation. J Neurosci 20(4):1435-1445
205. Giaume C, Theis M (2010) Pharmacological and genetic approaches to study connexin-mediated channels in glial cells of the central nervous system. Brain Res Rev 63(1-2):160-176. doi: 10.1016/j.brainresrev.2009.11.005
206. Blomstrand F, Aberg ND, Eriksson PS, Hansson E, Ronnback L (1999) Extent of intercellular calcium wave propagation is related to gap junction permeability and level of connexin-43 expression in astrocytes in primary cultures from four brain regions. Neuroscience 92(1):255-265
207. Rouach N, Glowinski J, Giaume C (2000) Activity-dependent neuronal control of gap-junctional communication in astrocytes. The Journal of cell biology 149(7):1513-1526
208. Roux L, Benchenane K, Rothstein JD, Bonvento G, Giaume C (2011) Plasticity of astroglial networks in olfactory glomeruli. Proc Natl Acad Sci USA 108(45):18442-18446
209. Giaume C, Tabernero A, Medina JM (1997) Metabolic trafficking through astrocytic gap junctions. Glia 21(1):114-123
210. Nedergaard M (1994) Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. Science 263(5154):1768-1771
211. Leybaert L, Paemeleire K, Strahonja A, Sanderson MJ (1998) Inositol-trisphosphate-dependent intercellular calcium signaling in and between astrocytes and endothelial cells. Glia 24(4):398-407
212. Froes MM, Correia AH, Garcia-Abreu J, Spray DC, Campos de Carvalho AC, Neto MV (1999) Gap-junctional coupling between neurons and astrocytes in primary central nervous system cultures. Proc Natl Acad Sci USA 96(13):7541-7546
213. Rash JE, Yasumura T, Davidson KG, Furman CS, Dudek FE, Nagy JI (2001) Identification of cells expressing Cx43, Cx30, Cx26, Cx32 and Cx36 in gap junctions of rat brain and spinal cord. Cell Commun Adhes 8(4-6):315-320
214. Porter JT, McCarthy KD (1997) Astrocytic neurotransmitter receptors in situ and in vivo. Prog Neurobiol 51(4):439-455
215. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369(6483):744-747. doi: 10.1038/369744a0
216. Newman EA (2001) Calcium signaling in retinal glial cells and its effect on neuronal activity. Prog Brain Res 132:241-254. doi: 10.1016/S0079-6123(01)32080-0
217. Fiacco TA, McCarthy KD (2006) Astrocyte calcium elevations: properties, propagation, and effects on brain signaling. Glia 54(7):676-690. doi: 10.1002/glia.20396
218. Bezzi P, Carmignoto G, Pasti L, Vesce S, Rossi D, Rizzini BL, Pozzan T, Volterra A (1998) Prostaglandins stimulate calcium-dependent glutamate release in astrocytes. Nature 391(6664):281-285. doi: 10.1038/34651
219. Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43(5):729-743. doi: 10.1016/j.neuron.2004.08.011
220. Angulo MC, Kozlov AS, Charpak S, Audinat E (2004) Glutamate released from glial cells synchronizes neuronal activity in the hippocampus. J Neurosci 24(31):6920-6927. doi: 10.1523/JNEUROSCI.0473-04.2004
221. Haydon PG, Carmignoto G (2006) Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev 86(3):1009-1031. doi: 10.1152/physrev.00049.2005
222. Parpura V, Baker BJ, Jeras M, Zorec R (2010) Regulated exocytosis in astrocytic signal integration. Neurochem Int 57(4):451-459. doi: 10.1016/j.neuint.2010.02.007
223. Araque A, Carmignoto G, Haydon PG, Oliet SH, Robitaille R, Volterra A (2014) Gliotransmitters travel in time and space. Neuron 81(4):728-739
224. 2+ detection and modulation of synaptic release by astrocytes. Nat Neurosci 14(10):1276-1284
225. Gordon GR, Iremonger KJ, Kantevari S, Ellis-Davies GC, MacVicar BA, Bains JS (2009) Astrocyte-mediated distributed plasticity at hypothalamic glutamate synapses. Neuron 64(3):391-403. doi: 10.1016/j.neuron.2009.10.021
226. Bonansco C, Couve A, Perea G, Ferradas CA, Roncagliolo M, Fuenzalida M (2011) Glutamate released spontaneously from astrocytes sets the threshold for synaptic plasticity. Eur J Neurosci 33(8):1483-1492
227. Lin JH, Lou N, Kang N, Takano T, Hu F, Han X, Xu Q, Lovatt D, Torres A, Willecke K, Yang J, Kang J, Nedergaard M (2008) A central role of connexin 43 in hypoxic preconditioning. J Neurosci 28(3):681-695
228. Li D, Agulhon C, Schmidt E, Oheim M, Ropert N (2013) New tools for investigating astrocyte-to-neuron communication. Front Cell Neurosci 7:193
229. Takano T, Tian GF, Peng W, Lou N, Libionka W, Han X, Nedergaard M (2006) Astrocyte-mediated control of cerebral blood flow. Nat Neurosci 9(2):260-267. doi: 10.1038/nn1623
230. Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann KA, Pozzan T, Carmignoto G (2003) Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 6(1):43-50. doi: 10.1038/nn980
231. Filosa JA, Bonev AD, Nelson MT (2004) Calcium dynamics in cortical astrocytes and arterioles during neurovascular coupling. Circ Res 95(10):e73-e81. doi: 10.1161/01.RES.0000148636.60732.2e
232. Koehler RC, Gebremedhin D, Harder DR (2006) Role of astrocytes in cerebrovascular regulation. J Appl Physiol 100(1):307-317. doi: 10.1152/japplphysiol.00938.2005
233. Schummers J, Yu H, Sur M (2008) Tuned responses of astrocytes and their influence on hemodynamic signals in the visual cortex. Science 320(5883):1638-1643. doi: 10.1126/science.1156120
234. 2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo. Proc Natl Acad Sci USA 110(48):E4678-E4687
235. Otsu Y, Couchman K, Lyons DG, Collot M, Agarwal A, Mallet JM, Pfrieger FW, Bergles DE, Charpak S (2015) Calcium dynamics in astrocyte processes during neurovascular coupling. Nat Neurosci 18(2):210-218
236. 2+ signaling. J Neurosci 26(5):1378-1385
237. Leybaert L, Sanderson MJ (2001) Intercellular calcium signaling and flash photolysis of caged compounds. A sensitive method to evaluate gap junctional coupling. Methods Mol Biol 154:407-430
238. Scemes E (2008) Modulation of astrocyte P2Y1 receptors by the carboxyl terminal domain of the gap junction protein Cx43. Glia 56(2):145-153. doi: 10.1002/glia.20598
239. Cornell-Bell AH, Finkbeiner SM, Cooper MS, Smith SJ (1990) Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science 247(4941):470-473
240. Smith SJ (1992) Do astrocytes process neural information? Prog Brain Res 94:119-136
241. Charles AC, Merrill JE, Dirksen ER, Sanderson MJ (1991) Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron 6(6):983-992
242. Arcuino G, Lin JH, Takano T, Liu C, Jiang L, Gao Q, Kang J, Nedergaard M (2002) Intercellular calcium signaling mediated by point-source burst release of ATP. Proc Natl Acad Sci USA 99(15):9840-9845. doi: 10.1073/pnas.152588599
243. Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CC, Nedergaard M (1998) Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA 95(26):15735-15740
244. Stout CE, Costantin JL, Naus CC, Charles AC (2002) Intercellular calcium signaling in astrocytes via ATP release through connexin hemichannels. J Biol Chem 277(12):10482-10488. doi: 10.1074/jbc.M109902200
245. Zanotti S, Charles A (1997) Extracellular calcium sensing by glial cells: low extracellular calcium induces intracellular calcium release and intercellular signaling. J Neurochem 69(2):594-602
246. Guthrie PB, Knappenberger J, Segal M, Bennett MV, Charles AC, Kater SB (1999) ATP released from astrocytes mediates glial calcium waves. J Neurosci 19(2):520-528
247. Harris-White ME, Zanotti SA, Frautschy SA, Charles AC (1998) Spiral intercellular calcium waves in hippocampal slice cultures. J Neurophysiol 79(2):1045-1052
248. 2+ waves and spreading depression in the mouse neocortex. J Neurosci 23(30):9888-9896
249. Schipke CG, Haas B, Kettenmann H (2008) Astrocytes discriminate and selectively respond to the activity of a subpopulation of neurons within the barrel cortex. Cereb Cortex 18(10):2450-2459. doi: 10.1093/cercor/bhn009
250. Willmott NJ, Wong K, Strong AJ (2000) Intercellular Ca(2+) waves in rat hippocampal slice and dissociated glial-neuron cultures mediated by nitric oxide. FEBS Lett 487(2):239-247
251. Hoogland TM, Kuhn B, Gobel W, Huang W, Nakai J, Helmchen F, Flint J, Wang SS (2009) Radially expanding transglial calcium waves in the intact cerebellum. Proc Natl Acad Sci USA 106(9):3496-3501. doi: 10.1073/pnas.0809269106
252. Nimmerjahn A, Kirchhoff F, Kerr JN, Helmchen F (2004) Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nat Methods 1(1):31-37. doi: 10.1038/nmeth706
253. 2+ signaling evoked by sensory stimulation in vivo. Nat Neurosci 9(6):816-823
254. Kuga N, Sasaki T, Takahara Y, Matsuki N, Ikegaya Y (2011) Large-scale calcium waves traveling through astrocytic networks in vivo. J Neurosci 31(7):2607-2614
255. Mathiesen C, Brazhe A, Thomsen K, Lauritzen M (2013) Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen. J Cereb Blood Flow Metab 33(2):161-169
256. Kurth-Nelson ZL, Mishra A, Newman EA (2009) Spontaneous glial calcium waves in the retina develop over early adulthood. J Neurosci 29(36):11339-11346
257. 2+ signaling in vivo. Glia 57(7):767-776
258. Kuchibhotla KV, Lattarulo CR, Hyman BT, Bacskai BJ (2009) Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 323(5918):1211-1215. doi: 10.1126/science.1169096
259. Crowe SE, Kantevari S, Ellis-Davies GC (2010) Photochemically initiated intracellular astrocytic calcium waves in living mice using two-photon uncaging of IP(3). ACS Chem Neurosci 1(8):575-585
260. 2+ waves transmit brain-damage signals to microglia. Dev Cell 22(6):1138-1148
261. Choo AM, Miller WJ, Chen YC, Nibley P, Patel TP, Goletiani C, Morrison B 3rd, Kutzing MK, Firestein BL, Sul JY, Haydon PG, Meaney DF (2013) Antagonism of purinergic signalling improves recovery from traumatic brain injury. Brain 136(Pt 1):65-80
262. 2+ signals contribute to neuronal excitotoxicity after status epilepticus. J Neurosci 27(40):10674-10684. doi: 10.1523/JNEUROSCI.2001-07.2007
263. Tian GF, Azmi H, Takano T, Xu Q, Peng W, Lin J, Oberheim N, Lou N, Wang X, Zielke HR, Kang J, Nedergaard M (2005) An astrocytic basis of epilepsy. Nat Med 11(9):973-981
264. Chuquet J, Hollender L, Nimchinsky EA (2007) High-resolution in vivo imaging of the neurovascular unit during spreading depression. J Neurosci 27(15):4036-4044
265. Sahlender DA, Savtchouk I, Volterra A (2014) What do we know about gliotransmitter release from astrocytes? Philos Trans R Soc Lond B Biol Sci 369(1654):20130592
266. Montero TD, Orellana JA (2015) Hemichannels: new pathways for gliotransmitter release. Neuroscience 286:45-59
267. Allard C, Carneiro L, Grall S, Cline BH, Fioramonti X, Chretien C, Baba-Aissa F, Giaume C, Penicaud L, Leloup C (2014) Hypothalamic astroglial connexins are required for brain glucose sensing-induced insulin secretion. J Cereb Blood Flow Metab 34(2):339-346
268. Orellana JA, Saez PJ, Cortes-Campos C, Elizondo RJ, Shoji KF, Contreras-Duarte S, Figueroa V, Velarde V, Jiang JX, Nualart F, Saez JC, Garcia MA (2012) Glucose increases intracellular free Ca(2+) in tanycytes via ATP released through connexin 43 hemichannels. Glia 60(1):53-68
269. Stehberg J, Moraga-Amaro R, Salazar C, Becerra A, Echeverria C, Orellana JA, Bultynck G, Ponsaerts R, Leybaert L, Simon F, Saez JC, Retamal MA (2011) Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala. Faseb J 26(9):3649-3657
270. 2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. J Physiol 588(Pt 20):3901-3920
271. Torres A, Wang F, Xu Q, Fujita T, Dobrowolski R, Willecke K, Takano T, Nedergaard M (2012) Extracellular Ca(2)(+) acts as a mediator of communication from neurons to glia. Sci Signal 5 (208):ra8. doi: 10.1126/scisignal.2002160
272. Chever O, Lee CY, Rouach N (2014) Astroglial connexin-43 hemichannels tune basal excitatory synaptic transmission. J Neurosci 34(34):11228-11232
273. Chever O, Pannasch U, Ezan P, Rouach N (2014) Astroglial connexin 43 sustains glutamatergic synaptic efficacy. Philos Trans R Soc Lond B Biol Sci 369(1654):20130596
274. Heinrich A, Ando RD, Turi G, Rozsa B, Sperlagh B (2012) K + depolarization evokes ATP, adenosine and glutamate release from glia in rat hippocampus: a microelectrode biosensor study. Br J Pharmacol 167(5):1003-1020
275. Pan HC, Chou YC, Sun SH (2015) P2X7 R-mediated Ca(2+) -independent d-serine release via pannexin-1 of the P2X7 R-pannexin-1 complex in astrocytes. Glia 63(5):877-893
276. Theis M, Jauch R, Zhuo L, Speidel D, Wallraff A, Doring B, Frisch C, Sohl G, Teubner B, Euwens C, Huston J, Steinhauser C, Messing A, Heinemann U, Willecke K (2003) Accelerated hippocampal spreading depression and enhanced locomotory activity in mice with astrocyte-directed inactivation of connexin-43. J Neurosci 23(3):766-776
277. Frisch C, Theis M, De Souza Silva MA, Dere E, Sohl G, Teubner B, Namestkova K, Willecke K, Huston JP (2003) Mice with astrocyte-directed inactivation of connexin-43 exhibit increased exploratory behaviour, impaired motor capacities, and changes in brain acetylcholine levels. Eur J Neurosci 18(8):2313-2318
278. Han Y, Yu HX, Sun ML, Wang Y, Xi W, Yu YQ (2014) Astrocyte-restricted disruption of connexin-43 impairs neuronal plasticity in mouse barrel cortex. Eur J Neurosci 39(1):35-45
279. Pannasch U, Freche D, Dallerac G, Ghezali G, Escartin C, Ezan P, Cohen-Salmon M, Benchenane K, Abudara V, Dufour A, Lubke JH, Deglon N, Knott G, Holcman D, Rouach N (2014) Connexin 30 sets synaptic strength by controlling astroglial synapse invasion. Nat Neurosci 17(4):549-558
280. Qu C, Gardner P, Schrijver I (2009) The role of the cytoskeleton in the formation of gap junctions by Connexin 30. Exp Cell Res 315(10):1683-1692
281. Unger T, Bette S, Zhang J, Theis M, Engele J (2012) Connexin-deficiency affects expression levels of glial glutamate transporters within the cerebrum. Neurosci Lett 506(1):12-16
282. May D, Tress O, Seifert G, Willecke K (2013) Connexin-47 protein phosphorylation and stability in oligodendrocytes depend on expression of Connexin-43 protein in astrocytes. J Neurosci 33(18):7985-7996
283. Iacobas S, Iacobas DA (2010) Astrocyte proximity modulates the myelination gene fabric of oligodendrocytes. Neuron Glia Biol 6(3):157-169
284. Magnotti LM, Goodenough DA, Paul DL (2011) Functional heterotypic interactions between astrocyte and oligodendrocyte connexins. Glia 59(1):26-34
285. Li T, Giaume C, Xiao L (2014) Connexins-mediated glia networking impacts myelination and remyelination in the central nervous system. Mol Neurobiol 49(3):1460-1471
286. Domercq M, Perez-Samartin A, Aparicio D, Alberdi E, Pampliega O, Matute C (2010) P2X7 receptors mediate ischemic damage to oligodendrocytes. Glia 58(6):730-740
287. Sun JD, Liu Y, Yuan YH, Li J, Chen NH (2011) Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats. Neuropsychopharmacology 37(5):1305-1320
288. Xu HL, Mao L, Ye S, Paisansathan C, Vetri F, Pelligrino DA (2008) Astrocytes are a key conduit for upstream signaling of vasodilation during cerebral cortical neuronal activation in vivo. Am J Physiol Heart Circ Physiol 294(2):H622-H632. doi: 10.1152/ajpheart.00530.2007
289. Jiang H, Zhu AG, Mamczur M, Falck JR, Lerea KM, McGiff JC (2007) Stimulation of rat erythrocyte P2X7 receptor induces the release of epoxyeicosatrienoic acids. Br J Pharmacol 151(7):1033-1040
290. Olk S, Turchinovich A, Grzendowski M, Stuhler K, Meyer HE, Zoidl G, Dermietzel R (2010) Proteomic analysis of astroglial connexin-43 silencing uncovers a cytoskeletal platform involved in process formation and migration. Glia 58(4):494-505
291. Boulay AC, Saubamea B, Cisternino S, Mignon V, Mazeraud A, Jourdren L, Blugeon C, Cohen-Salmon M (2015) The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels. Front Cell Neurosci 9:9
292. Boulay AC, Mazeraud A, Cisternino S, Saubamea B, Mailly P, Jourdren L, Blugeon C, Mignon V, Smirnova M, Cavallo A, Ezan P, Ave P, Dingli F, Loew D, Vieira P, Chretien F, Cohen-Salmon M (2015) Immune quiescence of the brain is set by astroglial connexin 43. J Neurosci 35(10):4427-4439
293. Mulligan SJ, MacVicar BA (2004) Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431(7005):195-199. doi: 10.1038/nature02827
294. Hansen DB, Braunstein TH, Nielsen MS, MacAulay N (2014) Distinct permeation profiles of the connexin 30 and 43 hemichannels. FEBS Lett 588(8):1446-1457
295. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308(5726):1314-1318
296. Ransohoff RM, Perry VH (2009) Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27:119-145
297. Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91(2):461-553
298. Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10(11):1387-1394
299. Perry VH, Nicoll JA, Holmes C (2010) Microglia in neurodegenerative disease. Nat Rev Neurol 6(4):193-201
300. Murugan M, Ling EA, Kaur C (2013) Glutamate receptors in microglia. CNS Neurol Disord: Drug Targets 12(6):773-784
301. Farber K, Kettenmann H (2006) Purinergic signaling and microglia. Pflugers Arch 452(5):615-621
302. Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS (2010) Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature 467(7317):863-867
303. Qu Y, Misaghi S, Newton K, Gilmour LL, Louie S, Cupp JE, Dubyak GR, Hackos D, Dixit VM (2011) Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J Immunol 186(11):6553-6561
304. Ohsawa K, Sanagi T, Nakamura Y, Suzuki E, Inoue K, Kohsaka S (2012) Adenosine A3 receptor is involved in ADP-induced microglial process extension and migration. J Neurochem 121(2):217-227
305. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8(6):752-758
306. Kim JV, Dustin ML (2006) Innate response to focal necrotic injury inside the blood-brain barrier. J Immunol 177(8):5269-5277
307. 2+ waves trigger responses in microglial cells in brain slices. Faseb J 16(2):255-257. doi: 10.1096/fj.01-0514fje
308. Verderio C, Matteoli M (2001) ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-gamma. J Immunol 166(10):6383-6391
309. Samuels SE, Lipitz JB, Dahl G, Muller KJ (2010) Neuroglial ATP release through innexin channels controls microglial cell movement to a nerve injury. The Journal of general physiology 136(4):425-442
310. Mika T, Prochnow N (2012) Functions of connexins and large pore channels on microglial cells: the gates to environment. Brain Res 1487:16-24
311. Maezawa I, Jin LW (2010) Rett syndrome microglia damage dendrites and synapses by the elevated release of glutamate. J Neurosci 30(15):5346-5356
312. Dobrenis K, Chang HY, Pina-Benabou MH, Woodroffe A, Lee SC, Rozental R, Spray DC, Scemes E (2005) Human and mouse microglia express connexin-36, and functional gap junctions are formed between rodent microglia and neurons. J Neurosci Res 82(3):306-315
313. Eugenin EA, Eckardt D, Theis M, Willecke K, Bennett MV, Saez JC (2001) Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha. Proc Natl Acad Sci USA 98(7):4190-4195
314. Takeuchi H, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R, Sonobe Y, Mizuno T, Suzumura A (2006) Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem 281(30):21362-21368
315. Ma Y, Cao W, Wang L, Jiang J, Nie H, Wang B, Wei X, Ying W (2014) Basal CD38/cyclic ADP-ribose-dependent signaling mediates ATP release and survival of microglia by modulating connexin 43 hemichannels. Glia. doi: 10.1002/glia.22651
316. Wasseff SK, Scherer SS (2014) Activated microglia do not form functional gap junctions in vivo. J Neuroimmunol 269(1-2):90-93. doi: 10.1016/j.jneuroim.2014.02.005
317. Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333(6048):1456-1458
318. Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29(13):3974-3980
319. Tremblay ME, Lowery RL, Majewska AK (2010) Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8(11):e1000527
320. Li Y, Du XF, Du JL (2013) Resting microglia respond to and regulate neuronal activity in vivo. Commun Integr Biol 6(4):e24493
321. Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR 3rd, Lafaille JJ, Hempstead BL, Littman DR, Gan WB (2012) Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155(7):1596-1609
322. Fontainhas AM, Wang M, Liang KJ, Chen S, Mettu P, Damani M, Fariss RN, Li W, Wong WT (2011) Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission. PLoS One 6(1):e15973
323. Dissing-Olesen L, LeDue JM, Rungta RL, Hefendehl JK, Choi HB, MacVicar BA (2014) Activation of neuronal NMDA receptors triggers transient ATP-mediated microglial process outgrowth. J Neurosci 34(32):10511-10527
324. Hamby ME, Sofroniew MV (2010) Reactive astrocytes as therapeutic targets for CNS disorders. Neurotherapeutics 7(4):494-506
325. Tonkin RS, Mao Y, O'Carroll SJ, Nicholson LF, Green CR, Gorrie CA, Moalem-Taylor G (2015) Gap junction proteins and their role in spinal cord injury. Front Mol Neurosci 7:102
326. Chew SS, Johnson CS, Green CR, Danesh-Meyer HV (2010) Role of connexin-43 in central nervous system injury. Exp Neurol 225(2):250-261
327. Bargiotas P, Monyer H, Schwaninger M (2009) Hemichannels in cerebral ischemia. Curr Mol Med 9(2):186-194
328. Contreras JE, Sanchez HA, Veliz LP, Bukauskas FF, Bennett MV, Saez JC (2004) Role of connexin-based gap junction channels and hemichannels in ischemia-induced cell death in nervous tissue. Brain Res Brain Res Rev 47(1-3):290-303
329. Koulakoff A, Mei X, Orellana JA, Saez JC (1818) Giaume C (2012) Glial connexin expression and function in the context of Alzheimer's disease. Biochim Biophys Acta 8:2048-2057
330. Orellana JA, von Bernhardi R, Giaume C, Saez JC (2012) Glial hemichannels and their involvement in aging and neurodegenerative diseases. Rev Neurosci 23(2):163-177
331. Quintanilla RA, Orellana JA, von Bernhardi R (2013) Understanding risk factors for Alzheimer's disease: interplay of neuroinflammation, connexin-based communication and oxidative stress. Arch Med Res 43(8):632-644
332. Nakase T, Maeda T, Yoshida Y, Nagata K (2009) Ischemia alters the expression of connexins in the aged human brain. J Biomed Biotechnol 2009:147946
333. Ashpole NM, Chawla AR, Martin MP, Brustovetsky T, Brustovetsky N, Hudmon A (2013) Loss of calcium/calmodulin-dependent protein kinase II activity in cortical astrocytes decreases glutamate uptake and induces neurotoxic release of ATP. J Biol Chem 288(20):14599-14611. doi: 10.1074/jbc.M113.466235
334. Perez Velazquez JL, Frantseva MV, Naus CC (2003) Gap junctions and neuronal injury: protectants or executioners? Neuroscientist 9(1):5-9
335. O'Connor JJ (2013) Targeting tumour necrosis factor-alpha in hypoxia and synaptic signalling. Ir J Med Sci 182(2):157-162
336. Froger N, Orellana JA, Calvo CF, Amigou E, Kozoriz MG, Naus CC, Saez JC, Giaume C (2010) Inhibition of cytokine-induced connexin-43 hemichannel activity in astrocytes is neuroprotective. Mol Cell Neurosci 45(1):37-46
337. O'Carroll SJ, Gorrie CA, Velamoor S, Green CR, Nicholson LF (2013) Connexin-43 mimetic peptide is neuroprotective and improves function following spinal cord injury. Neurosci Res 75(3):256-267. doi: 10.1016/j.neures.2013.01.004
338. Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, Takano H, Moss SJ, McCarthy K, Haydon PG (2005) Astrocytic purinergic signaling coordinates synaptic networks. Science 310(5745):113-116. doi: 10.1126/science.1116916
339. Decrock E, Vinken M, De Vuyst E, Krysko DV, D'Herde K, Vanhaecke T, Vandenabeele P, Rogiers V, Leybaert L (2009) Connexin-related signaling in cell death: to live or let die? Cell Death Differ 16(4):524-536
340. Shestopalov VI, Slepak VZ (2014) Molecular pathways of pannexin1-mediated neurotoxicity. Front Physiol 5:23
341. Kanneganti TD, Lamkanfi M, Kim YG, Chen G, Park JH, Franchi L, Vandenabeele P, Nunez G (2007) Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin inflammasome independent of Toll-like receptor signaling. Immunity 26(4):433-443
342. Minkiewicz J, de Rivero Vaccari JP, Keane RW (2013) Human astrocytes express a novel NLRP2 inflammasome. Glia 61(7):1113-1121. doi: 10.1002/glia.22499
343. Meme W, Calvo CF, Froger N, Ezan P, Amigou E, Koulakoff A, Giaume C (2006) Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: potentiation by beta-amyloid. Faseb J 20(3):494-496
344. Xiong J, Burkovetskaya M, Karpuk N, Kielian T (2012) IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection. ASN Neuro 4(3):AN2012008
345. Zhang FF, Morioka N, Nakashima-Hisaoka K, Nakata Y (2013) Spinal astrocytes stimulated by tumor necrosis factor-alpha and/or interferon-gamma attenuate connexin 43-gap junction via c-jun terminal kinase activity. J Neurosci Res 91(6):745-756
346. Saez PJ, Shoji KF, Retamal MA, Harcha PA, Ramirez G, Jiang JX, von Bernhardi R, Saez JC (2013) ATP is required and advances cytokine-induced gap junction formation in microglia in vitro. Mediators Inflamm 2013:216402
347. Orellana JA, Busso D, Ramirez G, Campos M, Rigotti A, Eugenin J, von Bernhardi R (2014) Prenatal nicotine exposure enhances Cx43 and Panx1 unopposed channel activity in brain cells of adult offspring mice fed a high-fat/cholesterol diet. Front Cell Neurosci 8:403
348. Abudara V, Roux L, Dallerac G, Matias I, Dulong J, Mothet JP, Rouach N, Giaume C (2015) Activated microglia impairs neuroglial interaction by opening Cx43 hemichannels in hippocampal astrocytes. Glia 63(5):795-811
349. Homkajorn B, Sims NR, Muyderman H (2010) Connexin 43 regulates astrocytic migration and proliferation in response to injury. Neurosci Lett 486(3):197-201
350. Theodoric N, Bechberger JF, Naus CC, Sin WC (2012) Role of gap junction protein connexin-43 in astrogliosis induced by brain injury. PLoS One 7(10):e47311. doi: 10.1371/journal.pone.0047311
351. Wu Z, Xu H, He Y, Yang G, Liao C, Gao W, Liang M, He X (2013) Antisense oligodeoxynucleotides targeting connexin-43 reduce cerebral astrocytosis and edema in a rat model of traumatic brain injury. Neurol Res 35(3):255-262. doi: 10.1179/1743132813Y.0000000165
352. Zhang X, Cao B, Wang J, Liu J, Tung VO, Lam PK, Chan LL, Li Y (2013) Neurotoxicity and reactive astrogliosis in the anterior cingulate cortex in acute ciguatera poisoning. Neuromol Med 15(2):310-323. doi: 10.1007/s12017-013-8220-7
353. Ohsumi A, Nawashiro H, Otani N, Ooigawa H, Toyooka T, Yano A, Nomura N, Shima K (2006) Alteration of gap junction proteins (connexins) following lateral fluid percussion injury in rats. Acta Neurochir Suppl 96:148-150
354. Cronin M, Anderson PN, Cook JE, Green CR, Becker DL (2008) Blocking connexin-43 expression reduces inflammation and improves functional recovery after spinal cord injury. Mol Cell Neurosci 39(2):152-160
355. Theriault E, Frankenstein UN, Hertzberg EL, Nagy JI (1997) Connexin-43 and astrocytic gap junctions in the rat spinal cord after acute compression injury. J Comp Neurol 382(2):199-214
356. Haupt C, Witte OW, Frahm C (2007) Up-regulation of Connexin-43 in the glial scar following photothrombotic ischemic injury. Mol Cell Neurosci 35(1):89-99. doi: 10.1016/j.mcn.2007.02.005
357. Kozoriz MG, Bechberger JF, Bechberger GR, Suen MW, Moreno AP, Maass K, Willecke K, Naus CC (2010) The connexin-43 C-terminal region mediates neuroprotection during stroke. J Neuropathol Exp Neurol 69(2):196-206. doi: 10.1097/NEN.0b013e3181cd44df
358. Mei X, Ezan P, Giaume C, Koulakoff A (2010) Astroglial connexin immunoreactivity is specifically altered at beta-amyloid plaques in beta-amyloid precursor protein/presenilin1 mice. Neuroscience 171(1):92-105
359. Fonseca CG, Green CR, Nicholson LF (2002) Upregulation in astrocytic connexin 43 gap junction levels may exacerbate generalized seizures in mesial temporal lobe epilepsy. Brain Res 929(1):105-116
360. Takahashi DK, Vargas JR, Wilcox KS (2010) Increased coupling and altered glutamate transport currents in astrocytes following kainic-acid-induced status epilepticus. Neurobiol Dis 40(3):573-585. doi: 10.1016/j.nbd.2010.07.018
361. Kerr NM, Johnson CS, Zhang J, Eady EK, Green CR, Danesh-Meyer HV (2012) High pressure-induced retinal ischaemia reperfusion causes upregulation of gap junction protein connexin-43 prior to retinal ganglion cell loss. Exp Neurol 234(1):144-152
362. Frantseva MV, Kokarovtseva L, Naus CG, Carlen PL, MacFabe D, Perez Velazquez JL (2002) Specific gap junctions enhance the neuronal vulnerability to brain traumatic injury. J Neurosci 22(3):644-653
363. Huang C, Han X, Li X, Lam E, Peng W, Lou N, Torres A, Yang M, Garre JM, Tian GF, Bennett MV, Nedergaard M, Takano T (2012) Critical role of connexin 43 in secondary expansion of traumatic spinal cord injury. J Neurosci 32(10):3333-3338
364. Yoon JJ, Green CR, O'Carroll SJ, Nicholson LF (2010) Dose-dependent protective effect of connexin-43 mimetic peptide against neurodegeneration in an ex vivo model of epileptiform lesion. Epilepsy Res 92(2-3):153-162
365. 2+ homeostasis and cell death. J Neurochem 70(3):958-970
366. Nakase T, Fushiki S, Naus CC (2003) Astrocytic gap junctions composed of connexin 43 reduce apoptotic neuronal damage in cerebral ischemia. Stroke 34(8):1987-1993
367. Karpuk N, Burkovetskaya M, Fritz T, Angle A, Kielian T (2011) Neuroinflammation leads to region-dependent alterations in astrocyte gap junction communication and hemichannel activity. J Neurosci 31(2):414-425. doi: 10.1523/JNEUROSCI.5247-10.2011
368. Davidson JO, Green CR, Nicholson LF, O'Carroll SJ, Fraser M, Bennet L, Gunn AJ (2012) Connexin hemichannel blockade improves outcomes in a model of fetal ischemia. Ann Neurol 71(1):121-132
369. Orellana JA, Hernandez DE, Ezan P, Velarde V, Bennett MV, Giaume C, Saez JC (2010) Hypoxia in high glucose followed by reoxygenation in normal glucose reduces the viability of cortical astrocytes through increased permeability of connexin 43 hemichannels. Glia 58(3):329-343
370. Samoilova M, Wentlandt K, Adamchik Y, Velumian AA, Carlen PL (2008) Connexin 43 mimetic peptides inhibit spontaneous epileptiform activity in organotypic hippocampal slice cultures. Exp Neurol 210(2):762-775
371. Chen YS, Toth I, Danesh-Meyer HV, Green CR, Rupenthal ID (2013) Cytotoxicity and vitreous stability of chemically modified connexin-43 mimetic peptides for the treatment of optic neuropathy. J Pharm Sci 102(7):2322-2331
372. Haefliger JA, Nicod P, Meda P (2004) Contribution of connexins to the function of the vascular wall. Cardiovasc Res 62(2):345-356
373. Gabriels JE, Paul DL (1998) Connexin-43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin-37 and connexin-40 are more uniformly distributed. Circ Res 83(6):636-643
374. Little TL, Beyer EC, Duling BR (1995) Connexin 43 and connexin 40 gap junctional proteins are present in arteriolar smooth muscle and endothelium in vivo. Am J Physiol 268(2 Pt 2):H729-H739
375. Traub O, Hertlein B, Kasper M, Eckert R, Krisciukaitis A, Hulser D, Willecke K (1998) Characterization of the gap junction protein connexin-37 in murine endothelium, respiratory epithelium, and after transfection in human HeLa cells. Eur J Cell Biol 77(4):313-322
376. De Bock M, Wang N, Decrock E, Bol M, Gadicherla AK, Culot M, Cecchelli R, Bultynck G, Leybaert L (2013) Endothelial calcium dynamics, connexin channels and blood-brain barrier function. Prog Neurobiol 108:1-20
377. Nagasawa K, Chiba H, Fujita H, Kojima T, Saito T, Endo T, Sawada N (2006) Possible involvement of gap junctions in the barrier function of tight junctions of brain and lung endothelial cells. J Cell Physiol 208(1):123-132
378. Wilson AC, Clemente L, Liu T, Bowen RL, Meethal SV, Atwood CS (2008) Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochim Biophys Acta 1782(6):401-407
379. Burns AR, Phillips SC, Sokoya EM (2012) Pannexin protein expression in the rat middle cerebral artery. J Vasc Res 49(2):101-110
380. Kaneko Y, Tachikawa M, Akaogi R, Fujimoto K, Ishibashi M, Uchida Y, Couraud PO, Ohtsuki S, Hosoya K, Terasaki T (2015) Contribution of pannexin 1 and connexin 43 hemichannels to extracellular calcium-dependent transport dynamics in human blood-brain barrier endothelial cells. J Pharmacol Exp Ther 353(1):192-200
381. Bedner P, Steinhauser C (1818) Theis M (2012) Functional redundancy and compensation among members of gap junction protein families? Biochim Biophys Acta 8:1971-1984