Dissection of Synchronous Population Discharges In Vitro

Part of the Springer Series in Computational Neuroscience book series (NEUROSCI, volume 2)


Synchronous population activities are generated by neuronal circuits of most brain regions. Distinct behavioural states are associated with the emergence of oscillations such as the theta and gamma rhythms of the hippocampus (Bragin et al., 1995; Buzsaki et al., 1983; Leung, 1992). Sleep phases are recognized by distinct rhythmic synchronous patterns (Steriade and Timofeev, 2003). Neuronal synchrony is observed during perinatal development, in many brain structures including the hippocampus (Leinekugel et al., 1998), retina (Meister et al., 1991) and spinal cord (O’Donovan, 1999). Pathological neuronal synchronization is associated with several disease states including Parkinson (Levy et al., 2000) and the epilepsies (Jefferys, 1994). This list shows that synchrony is ubiquitous in the nervous system, observed in many areas with different spatial and temporal properties and physiological or pathological correlates. In this review, we will focus on epileptiform and allied activities generated in the hippocampal formation attempting to show how different techniques and methods of analysis have propelled recent progress.


Partial Event Stratum Pyramidale Leader Cell Partial Synchronization Synchronous Firing 


  1. Abeles M (1982) Quantification, smoothing, and confidence limits for single-unit histograms. J Neurosci Methods 5:317–325.PubMedCrossRefGoogle Scholar
  2. Agmon A, Connors BW (1991) Thalamocortical responses of mouse somatosensory (barrel) cortex in vitro. Neuroscience 41: 365–379.PubMedCrossRefGoogle Scholar
  3. Agmon A, Wells JE (2003) The role of the hyperpolarization-activated cationic current I(h) in the timing of interictal bursts in the neonatal hippocampus. J Neurosci 23: 3658–3668.PubMedGoogle Scholar
  4. Alarcon G, Garcia Seoane JJ, Binnie CD, Martin Miguel MC, Juler J, Polkey CE, Elwes RDC, Ortiz Blasco JM (1997) Origin and propagation of interictal discharges in the acute electrocorticogram. Implications for pathophysiology and surgical treatment of temporal lobe epilepsy. Brain 120: 2259–2282.PubMedCrossRefGoogle Scholar
  5. Anderson P, Bliss VP, Skrede KK (1971) Lamellar organization of hippocampal excitatory pathways. Exp Brain Res 13:222–238.Google Scholar
  6. Ankri N, Korn H (1999) A statistical method for correcting distortions of amplitude distribution histograms due to collisions of synaptic events. J Neurosci Methods 91:83–99.PubMedCrossRefGoogle Scholar
  7. Aradi I, Maccaferri G (2004) Cell type-specific synaptic dynamics of synchronized bursting in the juvenile CA3 rat hippocampus. J Neurosci 24:9681–9692.PubMedCrossRefGoogle Scholar
  8. Avoli M, D'Antuono M, Louvel J, Köhling R, Biagini G, Pumain R, D'Arcangelo G, Tancredi V (2002) Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro. Prog Neurobiol 68:167–207.PubMedCrossRefGoogle Scholar
  9. Bartos M, Vida I, Jonas P (2007) Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks. Nat Rev Neurosci 8:45–56.PubMedCrossRefGoogle Scholar
  10. Bikson M, Fox JE, Jefferys JG (2003) Neuronal aggregate formation underlies spatiotemporal dynamics of nonsynaptic seizure initiation. J Neurophysiol 89:2330–2333.PubMedCrossRefGoogle Scholar
  11. Borg-Graham LJ, Monier C, Fregnac Y (1998) Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 393:369–373.PubMedCrossRefGoogle Scholar
  12. Bourien J, Bartolomei F, Bellanger JJ, Gavaret M, Chauvel P, Wendling F (2005) A method to identify reproducible subsets of co-activated structures during interictal spikes. Application to intracerebral EEG in temporal lobe epilepsy, Clin Neurophysiol 116:443–455.PubMedCrossRefGoogle Scholar
  13. Bragin A, Jandó G, Nádasdy Z, Hetke J, Wise K, Buzsáki G (1995) Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat. J Neurosci 15:47–60.PubMedGoogle Scholar
  14. Brecht M, Schneider M, Sakmann B, Margrie TW (2004) Whisker movements evoked by stimulation of single pyramidal cells in rat motor cortex. Nature 427:704–710.PubMedCrossRefGoogle Scholar
  15. Brown EN, Kass RE, Mitra PP (2004) Multiple neural spike train data analysis: state-of-the-art and future challenges. Nat Neurosci 7:456–461.PubMedCrossRefGoogle Scholar
  16. Buzsaki G (1986) Hippocampal sharp waves: their origin and significance. Brain Res 398:242–252.PubMedCrossRefGoogle Scholar
  17. Buzsáki G (1989) Two-stage model of memory trace formation: a role for ‘noisy’ brain states. Neuroscience 31:551–570.PubMedCrossRefGoogle Scholar
  18. Buzsaki G, Eidelberg E (1983) Phase relations of hippocampal projection cells and interneurons to theta activity in the anesthetized rat. Brain Res 266:334–339.Google Scholar
  19. Chagnac-Amitai Y, Connors BW (1989) Synchronized excitation and inhibition driven by intrinsically bursting neurons in neocortex. J Neurophysiol 62:1149–1162.PubMedGoogle Scholar
  20. Cohen I, Huberfeld G, Miles R (2006, Feb 1) Emergence of disinhibition-induced synchrony in the CA3 region of the guinea pig hippocampus in vitro. J Physiol 570(Pt 3):583–594.PubMedCrossRefGoogle Scholar
  21. Cohen I, Miles R (2000) Contributions of intrinsic and synaptic activities to the generation of neuronal discharges in in vitro hippocampus. J Physiol 524:485–502.PubMedCrossRefGoogle Scholar
  22. Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R (2002). On the origin of interictal activity in human temporal lobe epilepsy in vitro. Science 298:1418–1421.PubMedCrossRefGoogle Scholar
  23. Colom LV, Saggau P (1994) Spontaneous interictal-like activity originates in multiple areas of the CA2–CA3 region of hippocampal slices. J Neurophysiol 71:1574–1585.PubMedGoogle Scholar
  24. Csicsvari J, Hirase H, Mamiya A, Buzsaki G (2000) Ensemble patterns of hippocampal CA3–CA1 neurons during sharp wave-associated population events. Neuron 28:585–594.PubMedCrossRefGoogle Scholar
  25. Daley D, Vere-Jones D (2003) An Introduction to the Theory of Point Process, 2nd ed. Springer-Verlag, New York.Google Scholar
  26. DeFelipe J (1999) Chandelier cells and epilepsy. Brain 122:1807–1822.PubMedCrossRefGoogle Scholar
  27. Deuchars J, West DC, Thomson AM (1994 Aug 1) Relationships between morphology and physiology of pyramid-pyramid single axon connections in rat neocortex in vitro. J Physiol 478(Pt 3):423–435.Google Scholar
  28. Dichter M, Spencer WA. (1969) Penicillin-induced interictal discharges from the cat hippocampus. II. Mechanisms underlying origin and restriction. J Neurophysiol 32:663–687.PubMedGoogle Scholar
  29. Engel J Jr, Wilson C, Bragin A (2003) Advances in understanding the process of epileptogenesis based on patient material: what can the patient tell us? Epilepsia 44 (Suppl 12):60–71.PubMedCrossRefGoogle Scholar
  30. Fedirchuk B, Wenner P, Whelan PJ, Ho S, Tabak J, O'Donovan MJ (1999) Spontaneous network activity transiently depresses synaptic transmission in the embryonic chick spinal cord. J Neurosci 19:2102–2112.PubMedGoogle Scholar
  31. Foffani G, Uzcategui YG, Gal B, Menendez de la Prida L (2007) Reduced spike-timing reliability correlates with the emergence of fast ripples in the rat epileptic hippocampus. Neuron 55: 930–941.PubMedCrossRefGoogle Scholar
  32. Fox JE, Bikson M, Jefferys JG (2007) The effect of neuronal population size on the development of epileptiform discharges in the low calcium model of epilepsy. Neurosci Lett 411: 158–161.PubMedCrossRefGoogle Scholar
  33. Gähwiler BH, Capogna M, Debanne D, McKinney RA, Thompson SM (1997) Organotypic slice cultures: a technique has come of age. Trends Neurosci 20:471–477.PubMedCrossRefGoogle Scholar
  34. Galarreta M, Hestrin S (1998) Frequency-dependent synaptic depression and the balance of excitation and inhibition in the neocortex. Nat Neurosci 1:587–594.PubMedCrossRefGoogle Scholar
  35. Gerstein GL, Perkel DH (1969) Simultaneously recorded trains of action potentials: analysis and functional interpretation. Science 164:828–830.PubMedCrossRefGoogle Scholar
  36. Gold C, Henze DA, Koch C, Buzsáki G (2006) On the origin of the extracellular action potential waveform: a modeling study. J Neurophysiol 95:3113–3128.PubMedCrossRefGoogle Scholar
  37. Goldensohn ES, Zablow L, Salazar A (1977) The penicillin focus. I. Distribution of potential at the cortical surface. Electroencephalogr Clin Neurophysiol 42:480–492.PubMedCrossRefGoogle Scholar
  38. Graf M, Niedermeyer E, Schiemann J, Uematsu S, Long DM (1984) Electrocorticography: information derived from intraoperative recordings during seizure surgery. Clin Electroencephalogr 15:83–91.PubMedGoogle Scholar
  39. Grzywacz NM, Sernagor E (2000) Spontaneous activity in developing turtle retinal ganglion cells: statistical analysis. Vis Neurosci 17:229–241.PubMedCrossRefGoogle Scholar
  40. Gutnick MJ, Connors BW, Prince DA (1982) Mechanisms of neocortical epileptogenesis in vitro. J Neurophysiol 48:1321–1335.PubMedGoogle Scholar
  41. Hablitz JJ (1984) Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors. J Neurophysiol 51:1011–1027.PubMedGoogle Scholar
  42. Hausser M, Clark BA (1997). Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 19:665–678.PubMedCrossRefGoogle Scholar
  43. Helmchen F, Svoboda K, Denk W, Tank DW (1999) In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons. Nat Neurosci 2:989–996.PubMedCrossRefGoogle Scholar
  44. Hubel DH (1957) Tungsten microelectrodes for recording single units. Science 125:549–555.PubMedCrossRefGoogle Scholar
  45. Jefferys JG (1994) Experimental neurobiology of epilepsies. Curr Opin Neurol 7:113–122.PubMedCrossRefGoogle Scholar
  46. Jensen MS, Yaari Y (1997) Role of intrinsic burst firing, potassium accumulation, and electrical coupling in the elevated potassium model of hippocampal epilepsy. J Neurophysiol 77: 1224–1233.PubMedGoogle Scholar
  47. Johnston D, Brown TH. (1984) The synaptic nature of the paroxysmal depolarizing shift in hippocampal neurons. Ann Neurol 16 Suppl:S65–S71.PubMedCrossRefGoogle Scholar
  48. Knowles WD, Traub RD, Strowbridge BW (1987) The initiation and spread of epileptiform bursts in the in vitro hippocampal slice. Neuroscience 21:441–455.PubMedCrossRefGoogle Scholar
  49. Latham PE, Richmond BJ, Nelson PG, Nirenberg S (2000) Intrinsic dynamics in neuronal networks. I. Theory. J Neurophysiol 83:808–827.PubMedGoogle Scholar
  50. Le Van Quyen M, Bragin A (2007) Analysis of dynamic brain oscillations: methodological advances. Trends Neurosci 30:365–367.CrossRefGoogle Scholar
  51. Leinekugel X, Khalilov I, Ben-Ari Y, Khazipov R (1998) Giant depolarizing potentials: the septal pole of the hippocampus paces the activity of the developing intact septohippocampal complex in vitro. J Neurosci 18:6349–6357.PubMedGoogle Scholar
  52. Leung LS (1992) Fast (beta) rhythms in the hippocampus: a review. Hippocampus 2:93–98.PubMedCrossRefGoogle Scholar
  53. Levy R, Hutchison WD, Lozano AM, Dostrovsky JO (2000) High-frequency synchronization of neuronal activity in the subthalamic nucleus of parkinsonian patients with limb tremor. J Neurosci 20:7766–7775.PubMedGoogle Scholar
  54. Li X, Cui D, Jiruska P, Fox JE, Yao X, Jefferys JG (2007) Synchronization measurement of multiple neuronal populations. J Neurophysiol 98:3341–3348.PubMedCrossRefGoogle Scholar
  55. Lueders H, Bustamante LA, Zablow L, Goldensohn ES (1981) The independence of closely spaced discrete experimental spike foci. Neurology 31:846–851.PubMedCrossRefGoogle Scholar
  56. Mann EO, Suckling JM, Hajos N, Greenfield SA, Paulsen O (2005) Perisomatic feedback inhibition underlies cholinergically induced fast network oscillations in the rat hippocampus in vitro. Neuron 45:105–117.PubMedCrossRefGoogle Scholar
  57. Meister M, Wong RO, Baylor DA, Shatz CJ (1991) Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina. Science 252:939–943.PubMedCrossRefGoogle Scholar
  58. Menendez de la Prida L (2006) Functional features of the rat subicular microcircuits studied in vitro. Behav Brain Res 174:198–205.CrossRefGoogle Scholar
  59. Menendez de la Prida L, Benavides-Piccione R, Sola R, Pozo MA (2002) Electrophysiological properties of interneurons from intraoperative spiking areas of epileptic human temporal neocortex. Neuroreport 13:1421–1425.CrossRefGoogle Scholar
  60. Menendez de la Prida L, Gal B (2004) Synaptic contributions to focal and widespread spatiotemporal dynamics in the isolated rat subiculum in vitro. J Neurosci 24:5525–5536.CrossRefGoogle Scholar
  61. Menendez de la Prida LM, Huberfeld G, Cohen I, Miles R. (2006) Threshold behavior in the initiation of hippocampal population bursts. Neuron 49:131–142.CrossRefGoogle Scholar
  62. Menendez de la Prida L, Pozo MA (2002) Excitatory and inhibitory control of epileptiform discharges in combined hippocampal/entorhinal cortical slices. Brain Res 940:27–35.CrossRefGoogle Scholar
  63. Menendez de la Prida LM, Sanchez-Andres JV (1999) Nonlinear frequency-dependent synchronization in the developing hippocampus. J Neurophysiol 82:202–208.Google Scholar
  64. Miles R, Traub RD, Wong RK (1988) Spread of synchronous firing in longitudinal slices from the CA3 region of the hippocampus. J Neurophysiol 60:1481–1496.PubMedGoogle Scholar
  65. Miles R, Wong RK (1983) Single neurones can initiate synchronized population discharge in the hippocampus. Nature 306:371–373.PubMedCrossRefGoogle Scholar
  66. Miles R, Wong RK (1986) Excitatory synaptic interactions between CA3 neurones in the guinea-pig hippocampus. J Physiol 373:397–418.PubMedGoogle Scholar
  67. Miles R, Wong RK (1987) Inhibitory control of local excitatory circuits in the guinea-pig hippocampus. J Physiol 388:611–629.PubMedGoogle Scholar
  68. Mody I, Lambert JD, Heinemann U (1987) Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. J urophysiol 57:869–888; Nature 429:717–723.Google Scholar
  69. Niedermeyer E, Rocca U (1972) The diagnostic significance of sleep electroencephalograms in temporal lobe epilepsy. A comparison of scalp and depth tracings. Eur Neurol 7:119–129.PubMedCrossRefGoogle Scholar
  70. O'Donovan MJ. (1999) The origin of spontaneous activity in developing networks of the vertebrate nervous system. Curr Opin Neurobiol 9:94–104.PubMedCrossRefGoogle Scholar
  71. Pastor J, Menendez de la Prida LM, Hernando V, Sola RG (2006) Voltage sources in mesial temporal lobe epilepsy recorded with foramen ovale electrodes. Clin Neurophysiol 117: 2604–2614.PubMedCrossRefGoogle Scholar
  72. Penfield W, Jasper H (1954) Epilepsy and the Functional Anatomy of the Human Brain. Boston, MA: Little, Brown & Co.Google Scholar
  73. Perez Velazquez JL, Carlen PL (1999) Synchronization of GABAergic interneuronal networks during seizure-like activity in the rat horizontal hippocampal slice. Eur J Neurosci 11: 4110–4118.CrossRefGoogle Scholar
  74. Perreault P, Avoli M (1991) Physiology and pharmacology of epileptiform activity induced by 4-aminopyridine in rat hippocampal slices. J Neurophysiol 65:771–785.PubMedGoogle Scholar
  75. Pinto DJ, Patrick SL, Huang WC, Connors BW (2005) Initiation, propagation, and termination of epileptiform activity in rodent neocortex in vitro involve distinct mechanisms. J Neurosci 25:8131–8140.PubMedCrossRefGoogle Scholar
  76. Pouille F, Scanziani M (2004) Routing of spike series by dynamic circuits in the hippocampus. Nature 429:717–723.PubMedCrossRefGoogle Scholar
  77. Prince DA, Wilder BJ. (1967) Control mechanisms in cortical epileptogenic foci. "Surround" inhibition. Arch Neurol 16:194–202.PubMedCrossRefGoogle Scholar
  78. Sanabria ER, Su H, Yaari Y (2001) Initiation of network bursts by Ca2+-dependent intrinsic bursting in the rat pilocarpine model of temporal lobe epilepsy. J Physiol 532:205–216.PubMedCrossRefGoogle Scholar
  79. Sanchez-Vives MV, McCormick DA (2000) Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat Neurosci 3:1027–1034.PubMedCrossRefGoogle Scholar
  80. Scanziani M, Gahwiler BH, Thompson SM (1991) Paroxysmal inhibitory potentials mediated by GABAB receptors in partially disinhibited rat hippocampal slice cultures. J Physiol 444: 375–396.PubMedGoogle Scholar
  81. Schneiderman JH (1986) Low concentrations of penicillin reveal rhythmic, synchronous synaptic potentials in hippocampal slice. Brain Res 398:231–241.PubMedCrossRefGoogle Scholar
  82. Schwartzkroin PA, Knowles WD (1984) Intracellular study of human epileptic cortex: in vitro maintenance of epileptiform activity? Science 223:709–712.PubMedCrossRefGoogle Scholar
  83. Schwartzkroin PA, Prince DA (1977) Penicillin-induced epileptiform activity in the hippocampal in vitro prepatation. Ann Neurol 1:463–469.PubMedCrossRefGoogle Scholar
  84. Sipilä ST, Huttu K, Soltesz I, Voipio J, Kaila K. (2005) Depolarizing GABA acts on intrinsically bursting pyramidal neurons to drive giant depolarizing potentials in the immature hippocampus. J Neurosci 25:5280–5289.PubMedCrossRefGoogle Scholar
  85. Somogyi P, Klausberger T (2005, Jan 1) Defined types of cortical interneurone structure space and spike timing in the hippocampus. J Physiol 562(Pt 1):9–26 (Epub 2004 Nov 11, Review).PubMedCrossRefGoogle Scholar
  86. Spruston N, Schiller Y, Stuart G, Sakmann B (1995) Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science 268:297–300.PubMedCrossRefGoogle Scholar
  87. Staley KJ, Bains JS, Yee A, Hellier J, Longacher JM (2001) Statistical model relating CA3 burst probability to recovery from burst-induced depression at recurrent collateral synapses. J Neurophysiol 86:2736–2747.PubMedGoogle Scholar
  88. Staley KJ, Longacher M, Bains JS, Yee A (1998). Presynaptic modulation of CA3 network activity. Nat Neurosci 1:201–209.PubMedCrossRefGoogle Scholar
  89. Staley KJ, Proctor WR (1999) Modulation of mammalian dendritic GABA(A) receptor function by the kinetics of Cl- and HCO3-transport. J Physiol 519:693–712.PubMedCrossRefGoogle Scholar
  90. Steriade M, Timofeev I (2003) Neuronal plasticity in thalamocortical networks during sleep and waking oscillations. Neuron 37:563–576.PubMedCrossRefGoogle Scholar
  91. Suzuki SS, Smith GK (1985) Single-cell activity and synchronous bursting in the rat hippocampus during waking behavior and sleep. Exp Neurol 89:71–89.PubMedCrossRefGoogle Scholar
  92. Tabak J, Rinzel J, O'Donovan MJ (2001) The role of activity-dependent network depression in the expression and self-regulation of spontaneous activity in the developing spinal cord. J Neurosci 21:8966–8978.PubMedGoogle Scholar
  93. Thomson SM, Gähwiler BH (1989) Activity-dependent disinhibition. I. Repetitive stimulation reduces IPSP driving force and conductance in the hippocampus in vitro. J Neurophysiol 61:501–511.Google Scholar
  94. Tóth K, Freund TF, Miles R. (1997) Disinhibition of rat hippocampal pyramidal cells by GABAergic afferents from the septum. J Physiol 500:463–474.PubMedGoogle Scholar
  95. Traub RD, Miles R (1991) Neuronal Networks of the Hippocampus. Cambridge University Press, New York.CrossRefGoogle Scholar
  96. Traub RD, Wong RK (1982, May 14) Cellular mechanism of neuronal synchronization in epilepsy. Science 216(4547):745–747.Google Scholar
  97. Traynelis SF, Dingledine R (1988) Potassium-induced spontaneous electrographic seizures in the rat hippocampal slice. J Neurophysiol 59:259–276.PubMedGoogle Scholar
  98. Trevelyan AJ, Sussillo D, Watson BO, Yuste R. (2006) Modular propagation of epileptiform activity: evidence for an inhibitory veto in neocortex. J Neurosci 26:12447–12455.PubMedCrossRefGoogle Scholar
  99. Wellmer J, Su H, Beck H, Yaari Y (2002) Long-lasting modification of intrinsic discharge properties in subicular neurons following status epilepticus. Eur J Neurosci 16:259–266.PubMedCrossRefGoogle Scholar
  100. Wenner P, O'Donovan MJ (2001) Mechanisms that initiate spontaneous network activity in the developing chick spinal cord. J Neurophysiol 86:1481–1498.PubMedGoogle Scholar
  101. Wittner L, Miles R (2007) Factors defining a pacemaker region for synchrony in the hippocampus. J Physiol 584:867–883.PubMedCrossRefGoogle Scholar
  102. Wong RK, Traub RD (1983) Synchronized burst discharge in disinhibited hippocampal slice. I. Initiation in CA2–CA3 region. J Neurophysiol 49:442–458.PubMedGoogle Scholar
  103. Ziburkus J, Cressman JR, Barreto E, Schiff SJ (2006) Interneuron and pyramidal cell interplay during in vitro seizure-like events. J Neurophysiol 95:3948–3954.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.INSERM UMRS975/CNRS UMR7225, CHU Pitié-SalpêtrièreParisFrance
  2. 2.Instituto Cajal, CSICMadridSpain
  3. 3.Instituto Cajal – CSICMadridSpain

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