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Dependence of Generation of Hippocampal CA1 Slow Oscillations on Electrical Synapses

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Abstract

Neuronal oscillations in the hippocampus are critical for many brain functions including learning and memory. The underlying mechanism of oscillation generation has been extensively investigated in terms of chemical synapses and ion channels. Recently, electrical synapses have also been indicated to play important roles, as reported in various brain areas in vivo and in brain slices. However, this issue remains to be further clarified, including in hippocampal networks. Here, using the completely isolated hippocampus, we investigated in vitro the effect of electrical synapses on slow CA1 oscillations (0.5 Hz–1.5 Hz) generated intrinsically by the hippocampus. We found that these oscillations were totally abolished by bath application of a general blocker of gap junctions (carbenoxolone) or a specific blocker of electrical synapses (mefloquine), as determined by whole-cell recordings in both CA1 pyramidal cells and fast-spiking cells. Our findings indicate that electrical synapses are required for the hippocampal generation of slow CA1 oscillations.

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References

  1. Buzsaki G. Hippocampal sharp wave-ripple: A cognitive biomarker for episodic memory and planning. Hippocampus 2015, 25: 1073–1188.

    PubMed  PubMed Central  Google Scholar 

  2. Marshall L, Born J. The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn Sci 2007, 11: 442–450.

    PubMed  Google Scholar 

  3. Burgess N, Barry C, O’Keefe J. An oscillatory interference model of grid cell firing. Hippocampus 2007, 17: 801–812.

    PubMed  PubMed Central  Google Scholar 

  4. Molle M, Born J. Slow oscillations orchestrating fast oscillations and memory consolidation. Prog Brain Res 2011, 193: 93–110.

    PubMed  Google Scholar 

  5. Bonifazi P, Goldin M, Picardo MA, Jorquera I, Cattani A, Bianconi G, et al. GABAergic hub neurons orchestrate synchrony in developing hippocampal networks. Science 2009, 326: 1419–1424.

    CAS  PubMed  Google Scholar 

  6. Wulff P, Ponomarenko AA, Bartos M, Korotkova TM, Fuchs EC, Bahner F, et al. Hippocampal theta rhythm and its coupling with gamma oscillations require fast inhibition onto parvalbumin-positive interneurons. Proc Natl Acad Sci U S A 2009, 106: 3561–3566.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Alford ST, Alpert MH. A synaptic mechanism for network synchrony. Front Cell Neurosci 2014, 8: 290.

    PubMed  PubMed Central  Google Scholar 

  8. Buzsaki G, Wang XJ. Mechanisms of gamma oscillations. Annu Rev Neurosci 2012, 35: 203–225.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Calabrese RL, De Schutter E. Motor-pattern-generating networks in invertebrates: modeling our way toward understanding. Trends Neurosci 1992, 15: 439–445.

    CAS  PubMed  Google Scholar 

  10. Belluardo N, Mudo G, Trovato-Salinaro A, Le Gurun S, Charollais A, Serre-Beinier V, et al. Expression of connexin36 in the adult and developing rat brain. Brain Res 2000, 865: 121–138.

    CAS  PubMed  Google Scholar 

  11. Posluszny A. The contribution of electrical synapses to field potential oscillations in the hippocampal formation. Front Neural Circuits 2014, 8: 32.

    PubMed  PubMed Central  Google Scholar 

  12. Bennett MV, Zukin RS. Electrical coupling and neuronal synchronization in the mammalian brain. Neuron 2004, 41: 495–511.

    CAS  PubMed  Google Scholar 

  13. Bissiere S, Zelikowsky M, Ponnusamy R, Jacobs NS, Blair HT, Fanselow MS. Electrical synapses control hippocampal contributions to fear learning and memory. Science 2011, 331: 87–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Allen K, Fuchs EC, Jaschonek H, Bannerman DM, Monyer H. Gap junctions between interneurons are required for normal spatial coding in the hippocampus and short-term spatial memory. J Neurosci 2011, 31: 6542–6552.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Konopacki J, Kowalczyk T, Golebiewski H. Electrical coupling underlies theta oscillations recorded in hippocampal formation slices. Brain Res 2004, 1019: 270–274.

    CAS  PubMed  Google Scholar 

  16. Bocian R, Posluszny A, Kowalczyk T, Golebiewski H, Konopacki J. The effect of carbenoxolone on hippocampal formation theta rhythm in rats: in vitro and in vivo approaches. Brain Res Bull 2009, 78: 290–298.

    CAS  PubMed  Google Scholar 

  17. Buhl DL, Harris KD, Hormuzdi SG, Monyer H, Buzsaki G. Selective impairment of hippocampal gamma oscillations in connexin-36 knock-out mouse in vivo. J Neurosci 2003, 23: 1013–1018.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Traub RD, Kopell N, Bibbig A, Buhl EH, LeBeau FE, Whittington MA. Gap junctions between interneuron dendrites can enhance synchrony of gamma oscillations in distributed networks. J Neurosci 2001, 21: 9478–9486.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Hormuzdi SG, Pais I, LeBeau FE, Towers SK, Rozov A, Buhl EH, et al. Impaired electrical signaling disrupts gamma frequency oscillations in connexin 36-deficient mice. Neuron 2001, 31: 487–495.

    CAS  PubMed  Google Scholar 

  20. Pais I, Hormuzdi SG, Monyer H, Traub RD, Wood IC, Buhl EH, et al. Sharp wave-like activity in the hippocampus in vitro in mice lacking the gap junction protein connexin 36. J Neurophysiol 2003, 89: 2046–2054.

    CAS  PubMed  Google Scholar 

  21. Deans MR, Gibson JR, Sellitto C, Connors BW, Paul DL. Synchronous activity of inhibitory networks in neocortex requires electrical synapses containing connexin36. Neuron 2001, 31: 477–485.

    CAS  PubMed  Google Scholar 

  22. Christie JM, Bark C, Hormuzdi SG, Helbig I, Monyer H, Westbrook GL. Connexin36 mediates spike synchrony in olfactory bulb glomeruli. Neuron 2005, 46: 761–772.

    CAS  PubMed  Google Scholar 

  23. Tseng SH, Tsai LY, Yeh SR. Induction of high-frequency oscillations in a junction-coupled network. J Neurosci 2008, 28: 7165–7173.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Galarreta M, Hestrin S. Spike transmission and synchrony detection in networks of GABAergic interneurons. Science 2001, 292: 2295–2299.

    CAS  PubMed  Google Scholar 

  25. Draguhn A, Traub RD, Schmitz D, Jefferys JG. Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro. Nature 1998, 394: 189–192.

    CAS  PubMed  Google Scholar 

  26. Xu Y, Wang L, Liu YZ, Yang Y, Xue X, Wang Z. GABAergic interneurons are required for generation of slow CA1 oscillation in rat hippocampus. Neurosci Bull 2016, 32: 363–373.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Wang Y, Liu YZ, Wang SY, Wang Z. In vivo whole-cell recording with high success rate in anaesthetized and awake mammalian brains. Mol Brain 2016, 9: 86.

    PubMed  PubMed Central  Google Scholar 

  28. Roux L, Madar A, Lacroix MM, Yi C, Benchenane K, Giaume C. Astroglial connexin 43 hemichannels modulate olfactory bulb slow oscillations. J Neurosci 2015, 35: 15339–15352.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Cao R, Jiang S, Duan L, Xiong YF, Gao B, Rao ZR. Hypertonic stimulation induces synthesis and release of glutamate in cultured rat hypothalamic astrocytes and C6 cells. Neurosci Bull 2008, 24: 359–366.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Pan F, Mills SL, Massey SC. Screening of gap junction antagonists on dye coupling in the rabbit retina. Vis Neurosci 2007, 24: 609–618.

    PubMed  PubMed Central  Google Scholar 

  31. Cruikshank SJ, Hopperstad M, Younger M, Connors BW, Spray DC, Srinivas M. Potent block of Cx36 and Cx50 gap junction channels by mefloquine. Proc Natl Acad Sci U S A 2004, 101: 12364–12369.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Colgin LL. Rhythms of the hippocampal network. Nat Rev Neurosci 2016, 17: 239–249.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhao ZF, Li XZ, Wan Y. Mapping the information trace in local field potentials by a computational method of two-dimensional time-shifting synchronization likelihood based on graphic processing unit acceleration. Neurosci Bull 2017, 33: 653–663.

    PubMed  PubMed Central  Google Scholar 

  34. Liu YZ, Wang Y, Shen W, Wang Z. Enhancement of synchronized activity between hippocampal CA1 neurons during initial storage of associative fear memory. J Physiol 2017, 595: 5327–5340.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Grienberger C, Chen X, Konnerth A. NMDA receptor-dependent multidendrite Ca(2+) spikes required for hippocampal burst firing in vivo. Neuron 2014, 81: 1274–1281.

    CAS  PubMed  Google Scholar 

  36. Zhan Y. Harnessing GABAergic transmission for slow oscillations. Neurosci Bull 2016, 32: 501–502.

    PubMed  PubMed Central  Google Scholar 

  37. Kang J, Chen XL, Wang L, Rampe D. Interactions of the antimalarial drug mefloquine with the human cardiac potassium channels KvLQT1/minK and HERG. J Pharmacol Exp Ther 2001, 299: 290–296.

    CAS  PubMed  Google Scholar 

  38. Gribble FM, Davis TM, Higham CE, Clark A, Ashcroft FM. The antimalarial agent mefloquine inhibits ATP-sensitive K-channels. Br J Pharmacol 2000, 131: 756–760.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Maertens C, Wei L, Droogmans G, Nilius B. Inhibition of volume-regulated and calcium-activated chloride channels by the antimalarial mefloquine. J Pharmacol Exp Ther 2000, 295: 29–36.

    CAS  PubMed  Google Scholar 

  40. Alvarez-Maubecin V, Garcia-Hernandez F, Williams JT, Van Bockstaele EJ. Functional coupling between neurons and glia. J Neurosci 2000, 20: 4091–4098.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Venance L, Rozov A, Blatow M, Burnashev N, Feldmeyer D, Monyer H. Connexin expression in electrically coupled postnatal rat brain neurons. Proc Natl Acad Sci U S A 2000, 97: 10260–10265.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Buzsaki G. Electrical wiring of the oscillating brain. Neuron 2001, 31: 342–344.

    CAS  PubMed  Google Scholar 

  43. Cobb SR, Buhl EH, Halasy K, Paulsen O, Somogyi P. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 1995, 378: 75–78.

    CAS  PubMed  Google Scholar 

  44. Picardo MA, Guigue P, Bonifazi P, Batista-Brito R, Allene C, Ribas A, et al. Pioneer GABA cells comprise a subpopulation of hub neurons in the developing hippocampus. Neuron 2011, 71: 695–709.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Chang YY, Gong XW, Gong HQ, Liang PJ, Zhang PM, Lu QC. GABAA receptor activity suppresses the transition from inter-ictal to ictal epileptiform discharges in juvenile mouse hippocampus. Neurosci Bull 2018, 34: 1007–1016.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Zhu Q, Ke W, He Q, Wang X, Zheng R, Li T, et al. Laminar distribution of neurochemically-identified interneurons and cellular co-expression of molecular markers in epileptic human cortex. Neurosci Bull 2018, 34: 992–1006.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Condorelli DF, Belluardo N, Trovato-Salinaro A, Mudo G. Expression of Cx36 in mammalian neurons. Brain Res Brain Res Rev 2000, 32: 72–85.

    CAS  PubMed  Google Scholar 

  48. Stark E, Roux L, Eichler R, Senzai Y, Royer S, Buzsaki G. Pyramidal cell-interneuron interactions underlie hippocampal ripple oscillations. Neuron 2014, 83: 467–480.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Csicsvari J, Hirase H, Czurko A, Mamiya A, Buzsaki G. Oscillatory coupling of hippocampal pyramidal cells and interneurons in the behaving Rat. J Neurosci 1999, 19: 274–287.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (31471078, 91132711, and 30970960), and a Key Project of Shanghai Science and Technology Commission (15JC1400102 and 19ZR1416600).

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  1. Yuan Xu and Feng-Yan Shen have contributed equally to this work.

Authors and Affiliations

  1. Institute and Key Laboratory of Brain Functional Genomics of The Chinese Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, School of Life Sciences, East China Normal University, Shanghai, 200062, China

    Yuan Xu, Yu-Zhang Liu, Lidan Wang & Zhiru Wang

  2. Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, 200040, China

    Feng-Yan Shen & Ying-Wei Wang

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  1. Yuan Xu
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  2. Feng-Yan Shen
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  6. Zhiru Wang
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Correspondence to Zhiru Wang.

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Xu, Y., Shen, FY., Liu, YZ. et al. Dependence of Generation of Hippocampal CA1 Slow Oscillations on Electrical Synapses. Neurosci. Bull. 36, 39–48 (2020). https://doi.org/10.1007/s12264-019-00419-z

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