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A network of electrically coupled interneurons drives synchronized inhibition in neocortex

Nature Neuroscience volume 3, pages 904–910 (2000)Cite this article

Abstract

The neocortex has at least two different networks of electrically coupled inhibitory interneurons: fast-spiking (FS) and low-threshold-spiking (LTS) cells. Agonists of metabotropic glutamate or acetylcholine receptors induced synchronized spiking and membrane fluctuations, with irregular or rhythmic patterns, in networks of LTS cells. LTS activity was closely correlated with inhibitory postsynaptic potentials in neighboring FS interneurons and excitatory neurons. Synchronized LTS activity required electrical synapses, but not fast chemical synapses. Tetanic stimulation of local circuitry induced effects similar to those of metabotropic agonists. We conclude that an electrically coupled network of LTS interneurons can mediate synchronized inhibition when activated by modulatory neurotransmitters.

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Figure 1: Two networks of inhibitory interneurons in neocortex.
Figure 2: Synchronous activity in LTS cells.
Figure 3: Synchronized subthreshold oscillations of LTS cells did not require chemical synaptic transmission or action potentials.
Figure 4: Synchronous, rhythmic IPSPs induced by ACPD in FS and RS cells.
Figure 5: Muscarine-evoked synchrony.
Figure 6: Synchrony declines with distance.
Figure 7: Endogenous neuromodulators also trigger synchronous oscillations.

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References

  1. Holt, G. R., Softky, W. R., Koch, C. & Douglas, R. J. Comparison of discharge variability in vitro and in vivo in cat visual cortex neurons . J. Neurophysiol. 75, 1806– 1814 (1996).

    Article  CAS  Google Scholar 

  2. Gray, C. M. The temporal correlation hypothesis of visual feature integration: still alive and well. Neuron 24, 31– 47 (1999).

    Article  CAS  Google Scholar 

  3. deCharms, R. C. & Merzenich, M. M. Primary cortical representation of sounds by the coordination of action-potential timing. Nature 381, 610–613 (1996).

    Article  CAS  Google Scholar 

  4. Donoghue, J. P., Sanes, J. N., Hatsopoulos, N. G. & Gaal, G. Neural discharge and local field potential oscillations in primate motor cortex during voluntary movements. J. Neurophysiol. 79, 159–173 (1998).

    Article  CAS  Google Scholar 

  5. Azouz, R. & Gray, C. M. Cellular mechanisms contributing to response variability of cortical neurons in vivo. J. Neurosci. 19, 2209–2223 (1999).

    Article  CAS  Google Scholar 

  6. Stevens, C. F. & Zador, A. M. Input synchrony and the irregular firing of cortical neurons. Nat. Neurosci. 1, 210–217 (1998).

    Article  CAS  Google Scholar 

  7. Lampl, I., Reichova, I. & Ferster, D. Synchronous membrane potential fluctuations in neurons of the cat visual cortex. Neuron 22, 361 –374 (1999).

    Article  CAS  Google Scholar 

  8. Steriade, M. Synchronized activities of coupled oscillators in the cerebral cortex and thalamus at different levels of vigilance. Cereb. Cortex 7, 583–604 (1997).

    Article  CAS  Google Scholar 

  9. Fisahn, A., Pike, F. G., Buhl, E. H. & Paulsen, O. Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro. Nature 394, 186–189 (1998).

    Article  CAS  Google Scholar 

  10. Buzsaki, G. & Chrobak, J. J. Temporal structure in spatially organized neuronal ensembles: a role for interneuronal networks. Curr. Opin. Neurobiol. 5, 504–510 (1995).

    Article  CAS  Google Scholar 

  11. Benardo, L. S. Recruitment of GABAergic inhibition and synchronization of inhibitory interneurons in rat neocortex. J. Neurophysiol. 77, 3134 –3144 (1997).

    Article  CAS  Google Scholar 

  12. Zhang, Y. et al. Slow oscillations (≤1 Hz) mediated by GABAergic interneuronal networks in rat hippocampus. J. Neurosci. 18, 9256–9268 (1998).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Traub, R. D., Jefferys, J. G. R. & Whittington, M. A. Fast Oscillations in Cortical Circuits (MIT Press, Cambridge, Massachusetts, 1999).

    Book  Google Scholar 

  15. Skinner, F. K., Zhang, L., Velazquez, J. L. & Carlen, P. L. Bursting in inhibitory interneuronal networks: A role for gap-junctional coupling . J. Neurophysiol. 81, 1274– 1283 (1999).

    Article  CAS  Google Scholar 

  16. Kawaguchi, Y. & Kubota, Y. GABAergic cell subtypes and their synaptic connections in rat frontal cortex. Cereb. Cortex. 7, 476–486 (1997).

    Article  CAS  Google Scholar 

  17. Somogyi, P., Tamas, G., Lujan, R. & Buhl, E. H. Salient features of synaptic organisation in the cerebral cortex. Brain Res. Rev. 26, 113–135 (1998).

    Article  CAS  Google Scholar 

  18. Gibson, J. R., Beierlein, M. & Connors, B. W. Two networks of electrically coupled inhibitory neurons in neocortex. Nature, 402, 75– 79 (1999).

    Article  CAS  Google Scholar 

  19. Galarreta, M. & Hestrin, S. A network of fast-spiking cells in the neocortex connected by electrical synapses. Nature 402, 72–75 (1999).

    Article  CAS  Google Scholar 

  20. Tamás, G., Buhl, E. H., Lörincz, A. & Somogyi, P. Proximally targeted GABAergic synapses and gap junctions synchronize cortical interneurons. Nat. Neurosci. 3, 366– 371 (2000).

    Article  Google Scholar 

  21. Thomson, A. M. Activity-dependent properties of synaptic transmission at two classes of connections made by rat neocortical pyramidal axons in vitro. J. Physiol (Lond.) 502, 131–147 (1997).

    Article  CAS  Google Scholar 

  22. Reyes, A. et al. Target-cell-specific facilitation and depression in neocortical circuits. Nat. Neurosci. 1, 279– 285 (1998).

    Article  CAS  Google Scholar 

  23. Kawaguchi, Y. Selective cholinergic modulation of cortical GABAergic cell subtypes. J. Neurophysiol. 78, 1743–1747 (1997).

    Article  CAS  Google Scholar 

  24. Kawaguchi, Y. & Shindou, T. Noradrenergic excitation and inhibition of GABAergic cell types in rat frontal cortex. J. Neurosci. 18, 6963–6976 (1998).

    Article  CAS  Google Scholar 

  25. Xiang, Z., Huguenard, J. R. & Prince, D. A. Cholinergic switching within neocortical inhibitory networks. Science 281, 985– 988 (1998).

    Article  CAS  Google Scholar 

  26. Baude, A. et al. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron 11, 771– 787 (1993).

    Article  CAS  Google Scholar 

  27. Schoepp, D. D. & Conn, P. J. Metabotropic glutamate receptors in brain function and pathology. Trends Pharmacol. Sci. 14, 13–20 (1993).

    Article  CAS  Google Scholar 

  28. Flint, A. C., Dammerman, R. S. & Kriegstein, A. R. Endogenous activation of metabotropic glutamate receptors in neocortical development causes neuronal calcium oscillations. Proc. Natl. Acad. Sci. USA 96, 12144– 12149 (1999).

    Article  CAS  Google Scholar 

  29. Yuste, R., Peinado, A. & Katz, L. C. Neuronal domains in developing neocortex. Science 257, 665–669 (1992).

    Article  CAS  Google Scholar 

  30. Kandler, K. & Katz, L. C. Coordination of neuronal activity in developing visual cortex by gap junction-mediated biochemical communication . J. Neurosci. 18, 1419– 1427 (1998).

    Article  CAS  Google Scholar 

  31. Wang, X. J. & Rinzel, J. Spindle rhythmicity in the reticularis thalami nucleus: synchronization among mutually inhibitory neurons. Neuroscience 53, 899–904 (1993).

    Article  CAS  Google Scholar 

  32. Van Vreeswijk, C., Abbott, L. F. & Ermentrout, G. B. When inhibition not excitation synchronizes neural firing. J. Comput. Neurosci. 1, 313– 321 (1994).

    Article  CAS  Google Scholar 

  33. Buhl, E. H., Tamas, G. & Fisahn, A. Cholinergic activation and tonic excitation induce persistent gamma oscillations in mouse somatosensory cortex in vitro. J. Physiol. (Lond.) 513, 117–126 (1998).

    Article  CAS  Google Scholar 

  34. Bennett, M. V. Gap junctions as electrical synapses. J. Neurocytol. 26, 349–366 (1997).

    Article  CAS  Google Scholar 

  35. Manor, Y., Rinzel, J., Segev, I. & Yarom, Y. Low-amplitude oscillations in the inferior olive: a model based on electrical coupling of neurons with heterogeneous channel densities. J. Neurophysiol. 77 , 2736–2752 (1997).

    Article  CAS  Google Scholar 

  36. Michelson, H. B. & Wong, R. K. Synchronization of inhibitory neurones in the guinea-pig hippocampus in vitro. J. Physiol. (Lond.) 477, 35–45 (1994).

    Article  CAS  Google Scholar 

  37. 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 

  38. 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  CAS  Google Scholar 

  39. Engel, A. K., Roelfsema, P. R., Fries, P., Brecht, M. & Singer, W. Role of the temporal domain for response selection and perceptual binding. Cereb. Cortex 7, 571–582 (1997).

    Article  CAS  Google Scholar 

  40. Hatsopoulos, N. G., Ojakangas, C. L., Paninski, L. & Donoghue, J. P. Information about movement direction obtained from synchronous activity of motor cortical neurons. Proc. Natl. Acad. Sci. USA 95, 15706–15711 (1998).

    Article  CAS  Google Scholar 

  41. Mainen, Z. F. & Sejnowski, T. J. Reliability of spike timing in neocortical neurons. Science 268, 1503 –1506 (1995).

    Article  CAS  Google Scholar 

  42. Häusser, M. & Clark, B. A. Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration . Neuron 19, 665–678 (1997).

    Article  Google Scholar 

  43. Agmon, A. & Connors, B. W. Thalamocortical responses of mouse somatosensory (barrel) cortex in vitro. Neuroscience 41, 365–379 (1991).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Yael Amitai and Michael Paradiso for comments and Saundra Patrick for technical assistance. This work was supported by a fellowship to M.B. from the Burroughs-Wellcome Trust, a fellowship to J.R.G. from NIH (NS10478) and grants to B.W.C. from NIH (NS25983 and DA12500).

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  1. Michael Beierlein and Jay R. Gibson: The first two authors contributed equally to this work

Authors and Affiliations

  1. Department of Neuroscience, Division of Biology & Medicine, Box 1953, Brown University, Rhode Island, 02912, Providence, USA

    Michael Beierlein, Jay R. Gibson & Barry W. Connors

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  1. Michael Beierlein
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  3. Barry W. Connors
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Correspondence to Barry W. Connors.

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Beierlein, M., Gibson, J. & Connors, B. A network of electrically coupled interneurons drives synchronized inhibition in neocortex. Nat Neurosci 3, 904–910 (2000). https://doi.org/10.1038/78809

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