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Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro

Abstract

Acetylcholine is vital for cognitive functions of the brain. Although its actions in the individual cell are known in some detail1, its effects at the network level are poorly understood2. The hippocampus, which receives a major cholinergic input from the medial septum/diagonal band3, is important in memory4,5 and exhibits network activity at 40 Hz during relevant behaviours6. Here we show that cholinergic activation is sufficient to induce 40-Hz network oscillations7 in the hippocampus in vitro. Oscillatory activity is generated spontaneously in the CA3 subfield and can persist for hours. During the oscillatory state, principal neurons fire action potentials that are phase-related to the extracellular oscillation, but each neuron fires in only a small proportion of the cycles. Both excitatory and inhibitory synaptic events participate during the network oscillation in a precise temporal pattern. These results indicate that subcortical cholinergic input can control hippocampal memory processing by inducing fast network oscillations.

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Figure 1: Generation and propagation of 40-Hz oscillations in hippocampal slices.
Figure 2: Pharmacological analysis of 40-Hz oscillations in the CA3 area.
Figure 3: Temporal relationship between intracellular events and local field oscillations in CA3.

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References

  1. McCormick, D. A. Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog. Neurobiol. 39, 337–388 (1992).

    Article  CAS  Google Scholar 

  2. Liljenström, H. & Hasselmo, M. E. Cholinergic modulation of cortical oscillatory dynamics. J.Neurophysiol. 74, 288–297 (1995).

    Article  Google Scholar 

  3. Shute, C. C. D. & Lewis, P. R. Cholinesterase-containing systems of the brain of the rat. Nature 199, 1160–1164 (1963).

    Article  ADS  CAS  Google Scholar 

  4. Morris, R. G. M., Garrud, P., Rawlins, J. N. P. & O'Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature 297, 681–683 (1982).

    Article  ADS  CAS  Google Scholar 

  5. Bliss, T. V. P. & Collingridge, G. L. Asynaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993).

    Article  ADS  CAS  Google Scholar 

  6. Bragin, A. et al. Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat. J. Neurosci. 15, 47–60 (1995).

    Article  CAS  Google Scholar 

  7. Whittington, M. A., Traub, R. D. & Jefferys, J. G. R. Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation. Nature 373, 612–615 (1995).

    Article  ADS  CAS  Google Scholar 

  8. Konopacki, J., MacIver, M. B., Bland, B. H. & Roth, S. H. Carbachol-induced EEG “theta” activity in hippocampal brain slices. Brain Res. 405, 196–198 (1987).

    Article  CAS  Google Scholar 

  9. Huerta, P. T. & Lisman, J. E. Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature 364, 723–725 (1993).

    Article  ADS  CAS  Google Scholar 

  10. Williams, J. H. & Kauer, J. A. Properties of carbachol-induced oscillatory activity in rat hippocampus. J. Neurophysiol. 78, 2631–2640 (1997).

    Article  CAS  Google Scholar 

  11. Fellous, J.-M., Johnston, T., Segal, M. & Lisman, J. E. in Proc. Comput. Neurosci. Meeting, Big Sky Montana, July 1997 (ed. Bower, J. M.) (Plenum, New York, in the press).

  12. Engel, A. K., Kreiter, A. K., König, P. & Singer, W. Synchronization of oscillatory neuronal responses between striate and extrastriate visual cortical areas of the cat. Proc. Natl Acad. Sci. USA 88, 6048–6052 (1991).

    Article  ADS  CAS  Google Scholar 

  13. Lytton, W. W. & Sejnowski, T. J. Simulations of cortical pyramidal neurons synchronized by inhibitory interneurons. J. Neurophysiol. 66, 1059–1079 (1991).

    Article  CAS  Google Scholar 

  14. Buhl, E. H., Halasy, K. & Somogyi, P. Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites. Nature 368, 823–828 (1994).

    Article  ADS  CAS  Google Scholar 

  15. Cobb, S. R., Buhl, E. H., Halasy, K., Paulsen, O. & Somogyi, P. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378, 75–78 (1995).

    Article  ADS  CAS  Google Scholar 

  16. Wilson, M. & Bower, J. M. Cortical oscillations and temporal interactions in a computer simulation of piriform cortex. J. Neurophysiol. 67, 981–995 (1992).

    Article  CAS  Google Scholar 

  17. Traub, R. D., Whittington, M. A., Colling, S. B., Buzsáki, G. & Jefferys, J. G. R. Analysis of gamma rhythms in the rat hippocampus in vitro and in vivo. J. Physiol. 493, 471–484 (1996).

    Article  CAS  Google Scholar 

  18. Bleakman, D. et al. Activity of 2,3-benzodiazepines at native rat and recombinant human glutamate receptors in vitro: stereospecificity and selectivity profiles. Neuropharmacol. 35, 1689–1702 (1996).

    Article  CAS  Google Scholar 

  19. Benardo, L. S. & Prince, D. A. Cholinergic excitation of mammalian hippocampal pyramidal cells. Brain Res. 249, 315–331 (1982).

    Article  CAS  Google Scholar 

  20. Cole, A. E. & Nicoll, R. A. Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells. Science 221, 1299–1301 (1983).

    Article  ADS  CAS  Google Scholar 

  21. Hasselmo, M. E. & Schnell, E. Laminar selectivity of the cholinergic suppression of synaptic transmission in rat hippocampal region CA1: computational modeling and brain slice physiology. J. Neurosci. 14, 3898–3914 (1994).

    Article  CAS  Google Scholar 

  22. Pitler, T. A. & Alger, B. E. Cholinergic excitation of GABAergic interneurons in the rat hippocampal slice. J. Physiol. 450, 127–142 (1992).

    Article  CAS  Google Scholar 

  23. Miles, R. Synaptic excitation of inhibitory cells by single CA3 hippocampal pyramidal cells of the guinea-pig in vitro. J. Physiol. 428, 61–77 (1990).

    Article  CAS  Google Scholar 

  24. Llinás, R. R. The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 242, 1654–1664 (1988).

    Article  ADS  Google Scholar 

  25. Gray, C. M. & McCormick, D. A. Chattering cells: superficial pyramidal neurons contributing to the generation of synchronous oscillations in the visual cortex. Science 274, 109–113 (1996).

    Article  ADS  CAS  Google Scholar 

  26. Cobb, S. R. et al. Synaptic effects of identified interneurons innervating both interneurons and pyramidal cells in the rat hippocampus. Neuroscience 79, 629–648 (1997).

    Article  CAS  Google Scholar 

  27. Jefferys, J. G. R., Traub, R. D. & Whittington, M. A. Neuronal networks for induced ‘40 Hz’ rhythms. Trends Neurosci. 19, 202–208 (1996).

    Article  CAS  Google Scholar 

  28. Freeman, W. J. Relation between unit activity and evoked potentials in prepyriform cortex of cats. J.Neurophysiol. 31, 337–348 (1968).

    Article  CAS  Google Scholar 

  29. Whittington, M. A., Traub, R. D., Faulkner, H. J., Stanford, I. M. & Jefferys, J. G. R. Recurrent excitatory postsynaptic potentials induced by synchronized fast cortical oscillations. Proc. Natl Acad. Sci. USA 94, 12198–12203 (1997).

    Article  ADS  CAS  Google Scholar 

  30. Traub, R. D., Miles, R. & Wong, R. K. S. Model of the origin of rhythmic population oscillations in the hippocampal slice. Science 243, 1319–1325 (1989).

    Article  ADS  CAS  Google Scholar 

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Acknowledgements

We thank P. Somogyi and A. D. Smith for comments on an earlier version of the manuscript. E.H.B. holds a Medical Research Fellowship at Corpus Christi College, Oxford, and O.P. is the Christopher Welch Junior Research Fellow at Wadham College, Oxford. This work was supported by the British Medical Research Council, and grants from The Wellcome Trust (to O.P.) and The Royal Society (to O.P.).

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Correspondence to André Fisahn.

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Fisahn, A., Pike, F., Buhl, E. et al. Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro. Nature 394, 186–189 (1998). https://doi.org/10.1038/28179

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