Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Frequency-dependent synaptic depression and the balance of excitation and inhibition in the neocortex

Nature Neuroscience volume 1, pages 587–594 (1998)Cite this article

Abstract

The stability of cortical neuron activity in vivo suggests that the firing rates of both excitatory and inhibitory neurons are dynamically adjusted. Using dual recordings from excitatory pyramidal neurons and inhibitory fast-spiking neurons in neocortical slices, we report that sustained activation by trains of several hundred presynaptic spikes resulted in much stronger depression of synaptic currents at excitatory synapses than at inhibitory ones. The steady-state synaptic depression was frequency dependent and reflected presynaptic function. These results suggest that inhibitory terminals of fast-spiking cells are better equipped to support prolonged transmitter release at a high frequency compared with excitatory ones. This difference in frequency-dependent depression could produce a relative increase in the impact of inhibition during periods of high global activity and promote the stability of cortical circuits.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Excitatory and inhibitory unitary PSCs showed different synaptic depression in response to sustained 20 Hz stimulation.
Figure 2: Frequency-dependent depression of unitary excitatory and inhibitory synaptic connections.
Figure 3: Excitatory synaptic connections among neurons located in layer II/III show stronger frequency-dependent depression than inhibitory ones.
Figure 4: Frequency-dependent synaptic depression in response to sustained burst stimulation was stronger at excitatory than at inhibitory unitary connections.
Figure 5: Presynaptic mechanisms and frequency-dependent depression.
Figure 6: The PSC amplitude recovered faster than the synaptic reserve.
Figure 7: Frequency dependence of the synaptic impact (PSC amplitude × action potential frequency) at excitatory and inhibitory synaptic connections.

Similar content being viewed by others

References

  1. Hubel, D. H. Single unit activity in striate cortex of unrestrained cats. J. Physiol. (Lond.) 147, 226–238 (1959).

    Article  CAS  Google Scholar 

  2. Mountcastle, V. B., Talbot, W. H., Sakata, H. & Hyvärinen, J. Cortical neuronal mechanisms in flutter-vibration studied in unanesthetized monkeys. Neuronal periodicity and frequency discrimination. J. Neurophysiol. 32, 452–458 (1969).

    Article  CAS  Google Scholar 

  3. Hubel, D. H. & Wiesel, T. N. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J. Physiol. (Lond.) 160, 106–154 ( 1962).

    Article  CAS  Google Scholar 

  4. Abeles, M. Corticonics. Neural Circuits of the Cerebral Cortex (Cambridge Univ. Press, Cambridge, 1991).

  5. Azouz, R., Gray, C. M., Nowak, L. G. & McCormick, D. A. Physiological properties of inhibitory interneurons in cat striate cortex. Cereb. Cortex 7, 534–545 (1997).

    Article  CAS  Google Scholar 

  6. White, E. L. Cortical Circuits (Birkhaüser, Boston, 1989).

    Book  Google Scholar 

  7. Silva, L. R., Amitai, Y. & Connors, B. W. Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons. Science 251, 432–435 (1991).

    Article  CAS  Google Scholar 

  8. Shadlen, M. N. & Newsome, W. T. Noise, neural codes and cortical organization. Curr. Opin. Neurobiol. 4, 569–579 (1994).

    Article  CAS  Google Scholar 

  9. 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 

  10. Somers, D. C. Nelson, S. B. & Sur, M. An emergent model of orientation selectivity in cat visual cortical simple cells. J. Neurosci. 15, 5448–5465 (1995).

    Article  CAS  Google Scholar 

  11. Douglas, R. J., Mahowald, M., Martin, K. A. & Stratford, K. J. The role of synapses in cortical computation. J. Neurocytol. 25, 893–911 (1996).

    Article  CAS  Google Scholar 

  12. Konig, P., Engel, A. K. & Singer, W. Integrator or coincidence detector? The role of the cortical neuron revisited. Trends Neurosci. 19, 130–137 (1996).

    Article  CAS  Google Scholar 

  13. Tsodyks, M. V. & Markram, H. The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. Proc. Natl. Acad. Sci. USA 94, 719–723 (1997).

    Article  CAS  Google Scholar 

  14. Abbott, L. F., Varela, J. A., Sen, K. & Nelson, S. B. Synaptic depression and cortical gain control. Science 275, 220–224 (1997).

    Article  CAS  Google Scholar 

  15. Gutnick, M. J., Connors, B. W. & Prince, D. A. Mechanisms of neocortical epileptogenesis in vitro. J. Neurophysiol. 48, 1321– 1335 (1982).

    Article  CAS  Google Scholar 

  16. Somogyi., P., Kisvárday, Z. F., Martin, K. A. & Whitteridge, D. Synaptic connections of morphologically identified and physiologically characterized large basket cells in the striate cortex of cat. Neuroscience 10, 261–294 (1983).

    Article  CAS  Google Scholar 

  17. Kawaguchi, Y. Groupings of nonpyramidal and pyramidal cells with specific physiological and morphological characteristics in rat frontal cortex. J. Neurophysiol. 69, 416–431 ( 1993).

    Article  CAS  Google Scholar 

  18. Thomson, A. M., West, D. C., Hahn, J. & Deuchars, J. Single axon IPSPs elicited in pyramidal cells by three classes of interneurones in slices of rat neocortex. J. Physiol. (Lond.) 496, 81–102 (1996).

    Article  CAS  Google Scholar 

  19. Tamás, G., Buhl, E. H. & Somogyi, P. Fast IPSPs elicited via multiple synaptic release sites by different types of GABAergic neurone in the cat visual cortex. J. Physiol. (Lond.) 500, 715–738 (1997).

    Article  Google Scholar 

  20. Thomson, A. M., Deuchars, J. & West, D. C. Single axon excitatory postsynaptic potentials in neocortical interneurons exhibit pronounced paired pulse facilitation. Neuroscience 54, 347–360 (1993).

    Article  CAS  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. D. et al. Target-cell-specific facilitation and depression in neocortical circuits. Nature Neurosci. 1, 279– 285 (1998).

    Article  CAS  Google Scholar 

  23. Markram, H., Tsodyks, M. & Wang, Y. Differential signaling via the same axon of neocortical pyramidal neurons. Proc. Natl. Acad. Sci. USA 95, 5323–5328 (1998).

    Article  CAS  Google Scholar 

  24. Porter, J. T. et al. Properties of bipolar VIPergic interneurones and their excitation by pyramidal neurons in the rat neocortex. Eur. J. Neurosci. (in press).

  25. Tarczy-Hornoch, K., Martin, K. A., Jack, J. J. & Stratford, K. J. Synaptic interactions between smooth and spiny neurones in layer 4 of cat visual cortex in vitro. J. Physiol. (Lond.) 508, 351–363 (1998).

    Article  CAS  Google Scholar 

  26. Zhang, S. & Trussell, L. O. Voltage clamp analysis of excitatory synaptic transmission in the avian nucleus magnocellularis. J. Physiol. (Lond.) 480, 123–136 (1994).

    Article  CAS  Google Scholar 

  27. Takahashi, M., Kovalchuk, Y. & Attwell, D. Pre- and postsynaptic determinants of EPSC waveform at cerebellar climbing fiber and parallel fiber to Purkinje cell synapses. J. Neurosci. 15, 5693– 5702 (1995).

    Article  CAS  Google Scholar 

  28. Larkman, A. U., Jack, J. J. & Stratford, K. J. Quantal analysis of excitatory synapses in rat hippocampal CA1 in vitro during low-frequency depression. J. Physiol. (Lond.) 505, 457–471 ( 1997).

    Article  CAS  Google Scholar 

  29. Partin, K. M., Patneau, D. K., Winters, C. A., Mayer, M. L. & Buonanno, A. Selective modulation of desensitization at AMPA versus kainate receptors by cyclothiazide and concanavalin A. Neuron 11, 1069–1082 ( 1993).

    Article  CAS  Google Scholar 

  30. Pouzat, C. & Hestrin, S. Developmental regulation of basket/stellate cell→Purkinje cell synapses in the cerebellum. J. Neurosci. 17, 9104–9112 ( 1997).

    Article  CAS  Google Scholar 

  31. Katz, B. Nerve, Muscle, and Synapse (McGraw Hill, New York, 1966).

    Google Scholar 

  32. Dobrunz, L. E. & Stevens, C. F. Heterogeneity of release probability, facilitation, and depletion at central synapses. Neuron 18, 995–1008 ( 1997).

    Article  CAS  Google Scholar 

  33. Liu, G. & Tsien, R. W. Properties of synaptic transmission at single hippocampal synaptic boutons. Nature 375, 404–408 (1995).

    Article  CAS  Google Scholar 

  34. Ryan, T. A. & Smith, S. J. Vesicle pool mobilization during action potential firing at hippocampal synapses. Neuron 14, 983–989 (1995).

    Article  CAS  Google Scholar 

  35. Stevens, C. F. & Tsujimoto, T. Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool. Proc. Natl. Acad. Sci. USA 92, 846–849 (1995).

    Article  CAS  Google Scholar 

  36. Shupliakov, O. et al. Synaptic vesicle endocytosis impaired by disruption of dynamin-H3 domain interactions. Science 276, 259–263 (1997).

    Article  CAS  Google Scholar 

  37. von Gersdorff, H. & Matthews, G. Depletion and replenishment of vesicle pools at a ribbon-type synaptic terminal. J. Neurosci. 17, 1919–1927 (1997).

    Article  CAS  Google Scholar 

  38. Neher, E. Vesicle pools and Ca2+ microdomains: New tools for understanding their roles in neurotransmitter release. Neuron 20, 389–399 (1998).

    Article  CAS  Google Scholar 

  39. Wu, L. G. & Betz, W. J. Kinetics of synaptic depression and vesicle recycling after tetanic stimulation of frog motor nerve terminals. Biophys. J. 74, 3003–3009 (1998).

    Article  CAS  Google Scholar 

  40. Klingauf, J, Kavalali, E. T. & Tsien, R. W. Kinetics and regulation of fast endocytosis at hippocampal synapses. Nature 394, 581– 585 (1998).

    Article  CAS  Google Scholar 

  41. Silver, R. A., Momiyama, A. & Cull-Candy, S. G. Locus of frequency-dependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre–Purkinje cell synapses. J. Physiol. (Lond.) 510, 881–902 (1998).

    Article  CAS  Google Scholar 

  42. Wang, C. & Zucker, R. S. Regulation of synaptic vesicle recycling by calcium and serotonin. Neuron 21, 155–167 (1998).

    Article  CAS  Google Scholar 

  43. Zucker, R. S. Short-term synaptic plasticity. Annu. Rev. Neurosci. 12, 13–31 (1989).

    Article  CAS  Google Scholar 

  44. Forsythe, I. D., Tsujimoto, T., Barnes-Davies, M., Cuttle, M. F. & Takahashi, T. Inactivation of presynaptic calcium current contributes to synaptic depression at a fast central synapse. Neuron 20, 797–807 ( 1998).

    Article  CAS  Google Scholar 

  45. Chance, F. S., Nelson, S. B. & Abbott, L. F. Synaptic depression and the temporal response characteristics of V1 cells. J. Neurosci. 18, 4785– 4799 (1998).

    Article  CAS  Google Scholar 

  46. Ohzawa, I., Sclar, G. & Freeman, R. D. Contrast gain control in the cat's visual system. J. Neurophysiol. 54, 651– 667 (1985).

    Article  CAS  Google Scholar 

  47. Moshon, J. A., Thompson, I. D. & Tolhurst, D. J. Spatial and temporal contrast sensitivity of neurones in areas 17 and 18 of the cat's visual cortex. J. Physiol. (Lond.) 283, 101–120 ( 1978).

    Article  Google Scholar 

  48. Hawken, M. J., Shapley, R. M. & Grosof, D. H. Temporal-frequency selectivity in monkey visual cortex. Vis. Neurosci. 13, 477– 492 (1996).

    Article  CAS  Google Scholar 

  49. Carandini, M. & Ferster, D. A tonic hyperpolarization underlying contrast adaptation in cat visual cortex. Science 276 , 949–952 (1997).

    Article  CAS  Google Scholar 

  50. Markram, H., Lübke, J., Frotscher, M., Roth, A. & Sakmann, B. Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. J. Physiol. (Lond.) 500, 409– 440 (1997).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Jeffry Isaacson and Pankaj Sah for their comments on the manuscript. This work was supported by NIH grant (S.H.) and a grant from the Spanish Ministry of Education and Science (M.G.).

Author information

Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of Tennessee, Memphis, 855 Monroe Ave., Memphis, 38163, Tennessee, USA

    Mario Galarreta & Shaul Hestrin

Authors
  1. Mario Galarreta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaul Hestrin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shaul Hestrin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Galarreta, M., Hestrin, S. Frequency-dependent synaptic depression and the balance of excitation and inhibition in the neocortex. Nat Neurosci 1, 587–594 (1998). https://doi.org/10.1038/2822

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/2822

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing