Skip to main content
SpringerLink
Log in

GABAA receptor-mediated modulation of neuronal activity propagation upon tetanic stimulation in rat hippocampal slices

  • Neuroscience
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Tetanic stimulation (100 Hz), which can induce long-term potentiation in synaptic connections in the hippocampal CA1 region, causes γ-aminobutyric acid (GABA)A receptor-mediated long-lasting depolarization of postsynaptic neurons. However, it is not clear how this stimulation modulates neuronal activity propagation. We studied tetanic burst-induced neuronal responses in the hippocampal CA1 region by using optical-recording methods employing a voltage-sensitive dye and focused on GABAA receptor-mediated modulation. We observed that burst stimulation induced long-lasting depolarization and progressive decrease in individual excitatory postsynaptic potentials (EPSPs). Both these effects were suppressed by picrotoxin, a GABAA receptor antagonist. Under whole-cell voltage-clamp conditions, we observed a long-lasting inhibitory current (IPSC) and a prominent progressive decrease in the amplitude of the excitatory postsynaptic current (EPSC). Further, picrotoxin inhibited the IPSC and the progressive decrease in EPSC. The optically recorded long-lasting depolarization and progressive decrease of EPSPs were strongly dependent on the distance between the recording electrode and the stimulation site. Optical recordings performed across a wide swatch of CA1 revealed that the decrease in activity propagation was followed by facilitation of propagation after recovery and that this facilitation also depended on GABAA receptors. Intense activation of GABAA receptors is a key factor shaping the spatiotemporal patterns of high-frequency stimulation-induced responses in the CA1 region.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Alger BE, Nicoll RA (1979) GABA-mediated biphasic inhibitory responses in hippocampus. Nature 281:315–317

    Article  CAS  PubMed  Google Scholar 

  2. Alger BE, Nicoll RA (1982) Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol (Lond) 328:125–141

    CAS  Google Scholar 

  3. Ang CW, Carlson GC, Coulter DA (2006) Massive and specific dysregulation of direct cortical input to the hippocampus in temporal lobe epilepsy. J Neurosci 26:11850–11856

    Article  CAS  PubMed  Google Scholar 

  4. Bai L, Huang X, Yang Q, Wu JY (2006) Spatiotemporal patterns of an evoked network oscillation in neocortical slices: coupled local oscillators. J Neurophysiol 96:2528–2538

    Article  PubMed  Google Scholar 

  5. Bartos M, Vida I, Jonas P (2007) Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks. Nat Rev Neurosci 8:45–56

    Article  CAS  PubMed  Google Scholar 

  6. Beau FENL, Alger BE (1998) Transient suppression of GABAA-receptor-mediated IPSPs after epileptiform burst discharges in CA1 pyramidal cells. J Neurophysiol 79:659–669

    CAS  PubMed  Google Scholar 

  7. Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R (2007) GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev 87:1215–1284

    Article  CAS  PubMed  Google Scholar 

  8. Blaesse P, Airaksinen MS, Rivera C, Kaila K (2009) Cation-chloride cotransporters and neuronal function. Neuron 61:820–838

    Article  CAS  PubMed  Google Scholar 

  9. Bliss TVP, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361:31–39

    Article  CAS  PubMed  Google Scholar 

  10. Bracci E, Vreugdenhil M, Hack SP, Jefferys JG (1999) On the synchronizing mechanisms of tetanically induced hippocampal oscillations. J Neurosci 19:8104–8113

    CAS  PubMed  Google Scholar 

  11. Broicher T, Bidmon H-J, Kamuf B, Coulon P, Gorji A, Pape H-C, Speckmann E-J, Budde T (2010) Thalamic afferent activation of supragranular layers in auditory cortex in vitro: a voltage sensitive dye study. Neuroscience 165:371–385

    Article  CAS  PubMed  Google Scholar 

  12. Buzsaki G, Horvath Z, Urioste R, Hetke J, Wise K (1992) High-frequency network oscillation in the hippocampus. Science 256:1025–1027

    Article  CAS  PubMed  Google Scholar 

  13. Buzsaki G, Leung LW, Vanderwolf CH (1983) Cellular bases of hippocampal EEG in the behaving rat. Brain Res 287:139–171

    CAS  PubMed  Google Scholar 

  14. Buzsaki G, Penttonen M, Nadasdy Z, Bragin A (1996) Pattern and inhibition-dependent invasion of pyramidal cell dendrites by fast spikes in the hippocampus in vivo. Proc Natl Acad Sci USA 93:9921–9925

    Article  CAS  PubMed  Google Scholar 

  15. Carriero G, Uva L, Gnatkovsky V, de Curtis M (2009) Distribution of the olfactory fiber input into the olfactory tubercle of the in vitro isolated guinea pig brain. J Neurophysiol 101:1613–1619

    Article  PubMed  Google Scholar 

  16. Chang PY, Jackson MB (2006) Heterogeneous spatial patterns of long-term potentiation in rat hippocampal slices. J Physiol 576:427–443

    Article  CAS  PubMed  Google Scholar 

  17. Cohen LB, Salzberg BM (1978) Optical measurement of membrane potential. Rev Physiol Biochem Pharmacol 83:35–88

    CAS  PubMed  Google Scholar 

  18. Coulter DA, Carlson GC (2007) Functional regulation of the dentate gyrus by GABA-mediated inhibition. Prog Brain Res 163:235–243

    Article  CAS  PubMed  Google Scholar 

  19. Davies CH, Collingridge GL (1993) The physiological regulation of synaptic inhibition by GABAB autoreceptors in rat hippocampus. J Physiol 472:245–265

    CAS  PubMed  Google Scholar 

  20. de Curtis M, Takashima I, Iijima T (1999) Optical recording of cortical activity after in vitro perfusion of cerebral arteries with a voltage-sensitive dye. Brain Res 837:314–319

    Article  PubMed  Google Scholar 

  21. Dudel J, Kuffler SW (1961) Presynaptic inhibition at the crayfish neuromuscular junction. J Physiol 155:543–562

    CAS  PubMed  Google Scholar 

  22. Eccles JC, Schmidt R, Willis WD (1963) Pharmacological studies on presynaptic inhibition. J Physiol 168:500–530

    CAS  PubMed  Google Scholar 

  23. Farrant M, Kaila K (2007) The cellular, molecular and ionic basis of GABA(A) receptor signalling. Prog Brain Res 160:59–87

    Article  CAS  PubMed  Google Scholar 

  24. Fries P, Nikolic D, Singer W (2007) The gamma cycle. Trends Neurosci 30:309–316

    Article  CAS  PubMed  Google Scholar 

  25. Fujiwara-Tsukamoto Y, Isomura Y, Imanishi M, Fukai T, Takada M (2007) Distinct types of ionic modulation of GABA actions in pyramidal cells and interneurons during electrical induction of hippocampal seizure-like network activity. Eur J Neurosci 25:2713–2725

    Article  PubMed  Google Scholar 

  26. Grinvald A, Hildesheim R (2004) VSDI: a new era in functional imaging of cortical dynamics. Nat Rev Neurosci 5:874–885

    Article  CAS  PubMed  Google Scholar 

  27. Grover LM, Lambert NA, Schwartzkroin PA, Teyler TJ (1993) Role of HCO3− ions in depolarizing GABAA receptor-mediated responses in pyramidal cells of rat hippocampus. J Neurophysiol 69:1541–1555

    CAS  PubMed  Google Scholar 

  28. Harris KD, Hirase H, Leinekugel X, Henze DA, Buzsaki G (2001) Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells. Neuron 32:141–149

    Article  CAS  PubMed  Google Scholar 

  29. Isomura Y, Fujiwara-Tsukamoto Y, Takada M (2003) Glutamatergic propagation of GABAergic seizure-like after discharge in the hippocampus in vitro. J Neurophysiol 90:2746–2751

    Article  CAS  PubMed  Google Scholar 

  30. Jang IS, Ito Y, Akaike N (2005) Feed-forward facilitation of glutamate release by presynaptic GABA(A) receptors. NeuroReport 135:737–748

    CAS  Google Scholar 

  31. Jang IS, Nakamura M, Ito Y, Akaike N (2006) Presynaptic GABAA receptors facilitate spontaneous glutamate release from presynaptic terminals on mechanically dissociated rat CA3 pyramidal neurons. NeuroReport 138:25–35

    CAS  Google Scholar 

  32. Kaila K, Lamsa K, Smirnov S, Taira T, Voipio J (1997) Long-lasting GABA-mediated depolarization evoked by high-frequency stimulation in pyramidal neurons of rat hippocampal slice is attributable to a network-driven, bicarbonate-dependent K+ transient. J Neurosci 17:7662–7672

    CAS  PubMed  Google Scholar 

  33. Kaila K, Voipio J (1987) Postsynaptic fall in intracellular pH induced by GABA-activated bicarbonate conductance. Nature 330:163–165

    Article  CAS  PubMed  Google Scholar 

  34. Kaila K, Voipio J, Paalasmaa P, Pasternack M, Deisz RA (1993) The role of bicarbonate in GABAA receptor-mediated IPSPs of rat neocortical neurones. J Physiol 464:273–289

    CAS  PubMed  Google Scholar 

  35. Kajiwara R, Takashima I, Mimura Y, Witter MP, Iijima T (2003) Amygdala input promotes spread of excitatory neural activity from perirhinal cortex to the entorhinal–hippocampal circuit. J Neurophysiol 89:2176–2184

    Article  PubMed  Google Scholar 

  36. Kajiwara R, Tominaga T, Takashima I (2007) Olfactory information converges in the amygdaloid cortex via the piriform and entorhinal cortices: observations in the guinea pig isolated whole-brain preparation. Eur J Neurosci 25:3648–3658

    Article  PubMed  Google Scholar 

  37. Kiritoshi T, Ikeda H, Murase K (2010) Long-term potentiation of neuronal excitation in the central nucleus of the rat amygdala revealed by imaging with a voltage-sensitive dye. Brain Res 1349C:32–34

    Article  Google Scholar 

  38. Koganezawa N, Taguchi A, Tominaga T, Ohara S, Tsutsui K, Witter MP, Iijima T (2008) Significance of the deep layers of entorhinal cortex for transfer of both perirhinal and amygdala inputs to the hippocampus. Neurosci Res 61:172–181

    Article  PubMed  Google Scholar 

  39. 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

    Article  CAS  PubMed  Google Scholar 

  40. Mann EO, Tominaga T, Ichikawa M, Greenfield SA (2005) Cholinergic modulation of the spatiotemporal pattern of hippocampal activity in vitro. Neuropharmacology 48:118–133

    Article  CAS  PubMed  Google Scholar 

  41. Mennerick S, Chisari M, Shu HJ, Taylor A, Vasek M, Eisenman LN, Zorumski CF (2010) Diverse voltage-sensitive dyes modulate GABAA receptor function. J Neurosci 30:2871–2879

    Article  CAS  PubMed  Google Scholar 

  42. Paulsen O, Sejnowski TJ (2006) From invertebrate olfaction to human cognition: emerging computational functions of synchronized oscillatory activity. J Neurosci 26:1661–1662

    Article  CAS  PubMed  Google Scholar 

  43. Payne JA, Rivera C, Voipio J, Kaila K (2003) Cation-chloride co-transporters in neuronal communication, development and trauma. Trends Neurosci 26:199–206

    Article  CAS  PubMed  Google Scholar 

  44. Perreault P, Avoli M (1989) Effects of low concentrations of 4-aminopyridine on CA1 pyramidal cells of the hippocampus. J Neurophysiol 61:953–970

    CAS  PubMed  Google Scholar 

  45. Ruiz A, Fabian-Fine R, Scott R, Walker MC, Rusakov DA, Kullmann DM (2003) GABAA receptors at hippocampal mossy fibers. Neuron 39:961–973

    Article  CAS  PubMed  Google Scholar 

  46. Santhakumar V, Voipio J, Kaila K, Soltesz I (2003) Post-traumatic hyperexcitability is not caused by impaired buffering of extracellular potassium. J Neurosci 23:5865–5876

    CAS  PubMed  Google Scholar 

  47. Sejnowski TJ, Paulsen O (2006) Network oscillations: emerging computational principles. J Neurosci 26:1673–1676

    Article  CAS  PubMed  Google Scholar 

  48. Sinha SR, Saggau P (1999) Optical recording from populations of neurons in brain slices. In: Windhorst U, Johansson H (eds) Modern techniques in neuroscience research. Springer, Berlin, p 459486

    Google Scholar 

  49. Sinha SR, Saggau P (2001) Imaging of 4-AP-induced, GABAA-dependent spontaneous synchronized activity mediated by the hippocampal interneuron network. J Neurophysiol 86:381–391

    CAS  PubMed  Google Scholar 

  50. Staley KJ, Proctor WR (1999) Modulation of mammalian dendritic GABA(A) receptor function by the kinetics of Cl− and HCO3− transport. J Physiol Lond 519:693–712

    Article  CAS  PubMed  Google Scholar 

  51. Staley KJ, Soldo BL, Proctor WR (1995) Ionic mechanisms of neuronal excitation by inhibitory GABAA receptors. Science 269:977–981

    Article  CAS  PubMed  Google Scholar 

  52. Stein V, Nicoll RA (2003) GABA generates excitement. Neuron 37:375–378

    Article  CAS  PubMed  Google Scholar 

  53. Taira T, Lamsa K, Kaila K (1997) Posttetanic excitation mediated by GABA(A) receptors in rat CA1 pyramidal neurons. J Neurophysiol 77:2213–2218

    CAS  PubMed  Google Scholar 

  54. Tominaga T, Tominaga Y, Ichikawa M (2001) Simultaneous multi-site recordings of neural activity with an inline multi-electrode array and optical measurement in rat hippocampal slices. Pflügers Arch Eur J Physiol 443:317–322

    Article  CAS  Google Scholar 

  55. Tominaga T, Tominaga Y, Ichikawa M (2002) Optical imaging of long-lasting depolarization on burst stimulation in area CA1 of rat hippocampal slices. J Neurophysiol 88:1523–1532

    PubMed  Google Scholar 

  56. Tominaga T, Tominaga Y, Yamada H, Matsumoto G, Ichikawa M (2000) Quantification of optical signals with electrophysiological signals in neural activities of Di-4-ANEPPS stained rat hippocampal slices. J Neurosci Methods 102:11–23

    Article  CAS  PubMed  Google Scholar 

  57. Tominaga Y, Ichikawa M, Tominaga T (2009) Membrane potential response profiles of CA1 pyramidal cells probed with voltage-sensitive dye optical imaging in rat hippocampal slices reveal the impact of GABA(A)-mediated feed-forward inhibition in signal propagation. Neurosci Res 64:152–161

    Article  CAS  PubMed  Google Scholar 

  58. Traub RD, Whittington MA, Stanford IM, Jefferys JGR (1996) A mechanism for generation of long-range synchronous fast oscillations in the cortex. Nature 383:621–624

    Article  CAS  PubMed  Google Scholar 

  59. Trigo FF, Marty A, Stell BM (2008) Axonal GABAA receptors. Eur J Neurosci 28:841–848

    Article  PubMed  Google Scholar 

  60. Tu B, Gu Z, Shen JX, Lamb PW, Yakel JL (2009) Characterization of a nicotine-sensitive neuronal population in rat entorhinal cortex. J Neurosci 29:10436–10448

    Article  CAS  PubMed  Google Scholar 

  61. Voipio J, Kaila K (2000) GABAergic excitation and K(+)-mediated volume transmission in the hippocampus. Prog Brain Res 125:329–338

    Article  CAS  PubMed  Google Scholar 

  62. Whittington MA, Stanford IM, Colling SB, Jefferys JGR, Traub RD (1997) Spatiotemporal patterns of gamma frequency oscillations tetanically induced in the rat hippocampal slice. J Physiol Lond 502:591–607

    Article  CAS  PubMed  Google Scholar 

  63. Wu JY, Guan L, Tsau Y (1999) Propagating activation during oscillations and evoked responses in neocortical slices. J Neurosci 19:5005–5015

    CAS  PubMed  Google Scholar 

  64. Ylinen A, Bragin A, Nadasdy Z, Jando G, Szabo I, Sik A, Buzsaki G (1995) Sharp wave-associated high-frequency oscillation (200-Hz) in the intact hippocampus—network and intracellular mechanisms. J Neurosci 15:30–46

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Michinori Ichikawa for his kind encouragement and help during the early phase of this work and Dr. Michael E. Barish for his critical comments on an earlier version of the manuscript.

Author information

Authors and Affiliations

  1. Department of Neurophysiology, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa, 769-2193, Japan

    Takashi Tominaga & Yoko Tominaga

  2. Laboratory for Dynamics of Emergent Intelligence, RIKEN Brain Science Institute (BSI), 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan

    Takashi Tominaga

Authors
  1. Takashi Tominaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoko Tominaga
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takashi Tominaga.

Additional information

Grant sponsor: MHLW Japan; grant number: HSR Grants H20-Kagaku-009

Electronic supplementary materials

Below is the link to the electronic supplementary material.

Supplementary movie s1.mpg

Movie of hippocampal CA1 optical recording showing the propagation of excitation induced by high-frequency (100 Hz) tetanic stimulation in a standard transverse in vitro slice preparation (top). APV (50 μM) was added to the perfusate. Note the incremental inhibition of individual responses with increasing number of pulses (bottom). SO-A stratum oriens–alveus, SP stratum pyramidale, SR stratum radiatum, STIM stimulating electrode in SR of proximal CA1. (MPG 1930 kb)

Supplementary movie s2.mpg

Movie depicting the propagation pattern of tetanus-induced excitation in CA1 after subtraction of the long-lasting depolarizing component (blue trace transformed by subtraction). After subtraction, the diminished propagation of individual responses is clearer. Same conditions as in Supplemental movie s1.mpg. (MPG 1552 kb)

Supplementary movie s3.mpg

Movie depicting delayed probe responses after cessation of tetanus and in the presence of picrotoxin (PiTX; 100 μM). In contrast to normal conditions, GABAA receptor antagonism greatly diminished the distance-dependent recovery and enhancement of responses elicited after tetanic stimulation ended. (MPG 2080 kb)

Supplementary movie s4.mpg

Movie depicting the propagation pattern of delayed probe responses after cessation of tetanus in CA1. Black trace in the bottom graph shows the delayed probe response recorded at a pixel in stratum radiatum superimposed on the initial part of the response to the tetanus (red trace). Inhibition of propagation was predominant around the stimulating site, while enhancement of propagation was predominant at distal sites. (MPG 2098 kb)

Supplementary movie s5.mpg

Movie depicting the effect of GABAA receptor antagonism on the propagation pattern of tetanus-induced excitation in CA1 (blue trace). Picrotoxin (PiTX; 100 μM) was added to the perfusate. The steep convergence of the response toward the stimulation site present under normal control conditions is mostly absent when GABAA receptors are antagonized, i.e., the response becomes more homogenous over a large area of CA1. (MPG 2094 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tominaga, T., Tominaga, Y. GABAA receptor-mediated modulation of neuronal activity propagation upon tetanic stimulation in rat hippocampal slices. Pflugers Arch - Eur J Physiol 460, 875–889 (2010). https://doi.org/10.1007/s00424-010-0870-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-010-0870-9

Keywords

Search

Navigation