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Two networks of electrically coupled inhibitory neurons in neocortex

Nature volume 402, pages 75–79 (1999)Cite this article

Abstract

Inhibitory interneurons are critical to sensory transformations, plasticity and synchronous activity in the neocortex1,2. There are many types of inhibitory neurons, but their synaptic organization is poorly understood. Here we describe two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons. Paired-cell recordings showed that inhibitory neurons of the same type were strongly interconnected by electrical synapses, but electrical synapses between different inhibitory cell types were rare. The electrical synapses were strong enough to synchronize spikes in coupled interneurons. Inhibitory chemical synapses were also common between FS cells, and between FS and LTS cells, but LTS cells rarely inhibited one another. Thalamocortical synapses, which convey sensory information to the cortex, specifically and strongly excited only the FS cell network. The electrical and chemical synaptic connections of different types of inhibitory neurons are specific, and may allow each inhibitory network to function independently.

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Figure 1: Two types of inhibitory interneurons.
Figure 2: Chemical synaptic connections of inhibitory interneurons.
Figure 3: Electrical synapses between interneurons.
Figure 4: Electrical synapses coupling the spiking activity of two interneurons.

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References

  1. 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 

  2. Jones,E. G. GABAergic neurons and their role in cortical plasticity in primates. Cerebral Cortex 3, 361–372 (1993).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Simons,D. J. & Woolsey,T. A. Morphology of Golgi-Cox-impregnated barrel neurons in rat SmI cortex. J. Comp. Neurol. 230, 119–132 (1984).

    Article  CAS  Google Scholar 

  5. Thomson,A. M. & Deuchars,J. Synaptic interactions in neocortical local circuits: dual intracellular recordings in vitro. Cereb. Cortex 7, 510–522 (1997).

    Article  CAS  Google Scholar 

  6. 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 

  7. Reyes,A. & Sakmann,B. Target-cell-specific facilitation and depression in neocortical circuits. Nature Neurosci. 1, 279–285 (1998).

    Article  CAS  Google Scholar 

  8. Connors,B. W. & Gutnick,M. J. Intrinsic firing patterns of diverse neocortical neurons. Trends Neurosci. 13, 99–104 (1990).

    Article  CAS  Google Scholar 

  9. Agmon,A. & Connors,B. W. Correlation between intrinsic firing patterns and thalamocortical synaptic responses of neurons in mouse barrel cortex. J. Neurosci. 12, 319–329 (1992).

    Article  CAS  Google Scholar 

  10. Swadlow,H. A., Beloozerova,I. N. & Sirota,M. G. Sharp, local synchrony among putative feed-forward inhibitory interneurons of rabbit somatosensory cortex. J. Neurophysiol. 79, 567–582 (1998).

    Article  CAS  Google Scholar 

  11. Staiger,J. F., Zilles,K. & Freund,T. F. Distribution of GABAergic elements postsynaptic to ventroposteromedial thalamic projections in layer IV of rat barrel cortex. Eur. J. Neurosci. 8, 2273–2285 (1996).

    Article  CAS  Google Scholar 

  12. Gil,Z., Connors,B. W. & Amitai,Y. Efficacy of thalamocortical and intracortical synaptic connections: quanta, innervation, and reliability. Neuron 23, 385–397 (1999).

    Article  CAS  Google Scholar 

  13. Connors,B. W., Benardo,L. S. & Prince,D. A. Coupling between neurons of the developing rat neocortex. J. Neurosci. 3, 773–782 (1983).

    Article  CAS  Google Scholar 

  14. Peinado,A., Yuste,R. & Katz,L. C. Extensive dye coupling between rat neocortical neurons during the period of circuit formation. Neuron 10, 103–114 (1993).

    Article  CAS  Google Scholar 

  15. 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 

  16. Sloper,J. J. & Powell,T. P. Gap junctions between dendrites and somata of neurons in the prime sensori-motor cortex. Proc. R. Soc. Lond. B 203, 39–47 (1978).

    Article  ADS  CAS  Google Scholar 

  17. Bozhilova-Pastirova,A. & Ovtscharoff,W. Structure of the synaptic junctions in the rat sensorimotor cortex: freeze-etching study of neuronal gap junctions. Neurosci. Lett. 201, 265–267 (1995).

    Article  CAS  Google Scholar 

  18. Bennett,M. V. L. in Handbook of Physiology, Section 1: The Nervous System, Part I (eds Brookhart, J. M. & Mountcastle, V. B.) 357–416 (American Physiological Society, Bethesda, 1977).

    Google Scholar 

  19. Dermietzel,R. & Spray,D. C. Gap junctions in the brain: where, what type, how many and why? Trends Neurosci. 16, 186–192 (1993).

    Article  CAS  Google Scholar 

  20. Jefferys,J. G. R. Nonsynaptic modulation of neuronal activity in the brain: electric currents and extracellular ions. Physiol. Rev. 75, 689–723 (1995).

    Article  CAS  Google Scholar 

  21. Johnston,M. F., Simon,S. A. & Ramon,F. Interaction of anesthetics with electrical synapses. Nature 286, 498–500 (1980).

    Article  ADS  CAS  Google Scholar 

  22. Veenstra,R. D. Size and selectivity of gap junction channels formed from different connexins. J. Bioenerg. Biomembr. 28, 327–337 (1996).

    Article  CAS  Google Scholar 

  23. Nadarajah,B., Jones,A. M., Evans,W. H. & Parnevelas,J. G. Differential expression of connexins during neocortical development and neuronal circuit formation. J. Neurosci. 17, 3096–3111 (1997).

    Article  CAS  Google Scholar 

  24. Christie,M. J., Williams,J. T. & North,R. A. Electrical coupling synchronizes subthreshold activity in locus coeruleus neurons in vitro from neonatal rats. J. Neurosci. 9, 3584–3589 (1989).

    Article  CAS  Google Scholar 

  25. Mann-Metzer,P. & Yarom,Y. Electrotonic coupling interacts with intrinsic properties to generate synchronized activity in cerebellar networks of inhibitory interneurons. J. Neurosci. 19, 3298–3306 (1999).

    Article  CAS  Google Scholar 

  26. 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 

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

    Article  CAS  Google Scholar 

  28. 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 

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

    Article  CAS  Google Scholar 

  30. Xiang,Z., Huguenard,J. R. & Prince,D. A. Cholinergic switching within neocortical inhibitory networks. Science 281, 985–988 (1999).

    Article  ADS  Google Scholar 

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Acknowledgements

We thank S. Patrick for technical assistance, Y. Amitai and M. Bear for comments on the manuscript, and R. Benoit for gifts of anti-somatostatin antibodies. This work was supported by a fellowship to J.R.G. from NIH and a grant to B.W.C. from NIH.

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Author notes

  1. Jay R. Gibson and Michael Beierlein: These authors contributed equally to this work

  2. Barry W. Connors: Correspondence and request for materials should be addressed to B.W.C.

Authors and Affiliations

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

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

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  1. Jay R. Gibson
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  2. Michael Beierlein
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  3. Barry W. Connors
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Correspondence to Barry W. Connors.

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Gibson, J., Beierlein, M. & Connors, B. Two networks of electrically coupled inhibitory neurons in neocortex. Nature 402, 75–79 (1999). https://doi.org/10.1038/47035

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