Skip to main content

Thank you for visiting 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.

Turning on and off recurrent balanced cortical activity


The vast majority of synaptic connections onto neurons in the cerebral cortex arise from other cortical neurons, both excitatory and inhibitory, forming local and distant ‘recurrent’ networks. Although this is a basic theme of cortical organization, its study has been limited largely to theoretical investigations, which predict that local recurrent networks show a proportionality or balance between recurrent excitation and inhibition, allowing the generation of stable periods of activity1,2,3,4,5. This recurrent activity might underlie such diverse operations as short-term memory4,6,7, the modulation of neuronal excitability with attention8,9, and the generation of spontaneous activity during sleep5,10,11,12,13,14. Here we show that local cortical circuits do indeed operate through a proportional balance of excitation and inhibition generated through local recurrent connections, and that the operation of such circuits can generate self-sustaining activity that can be turned on and off by synaptic inputs. These results confirm the long-hypothesized role of recurrent activity as a basic operation of the cerebral cortex.

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

Access options

Rent or buy this article

Prices vary by article type



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

Figure 1: Prefrontal cortical slices generate periods of recurrent activity both spontaneously and in response to electrical stimulation of the neuropil.
Figure 4: The UP state enhances neuronal responses to PSPs in pyramidal cells.
Figure 2: Recurrent activity is generated by a balanced barrage of IPSPs and EPSPs.
Figure 3: The UP state enhances neuronal responses to PSPs in FS interneurons.
Figure 5: Reversal potential of evoked responses for the start and stop stimuli.

Similar content being viewed by others


  1. Wang, X. J. Synaptic reverberation underlying mnemonic persistent activity. Trends Neurosci. 24, 455–463 (2001)

    Article  CAS  PubMed  Google Scholar 

  2. van Vreeswijk, C. & Sompolinsky, H. Chaotic balanced state in a model of cortical circuits. Neural Comput. 10, 1321–1371 (1998)

    Article  CAS  PubMed  Google Scholar 

  3. Shadlen, M. N. & Newsome, W. T. The variable discharge of cortical neurons: implications for connectivity, computation, and information coding. J. Neurosci. 18, 3870–3896 (1998)

    Article  CAS  PubMed  Google Scholar 

  4. Durstewitz, D., Seamans, J. K. & Sejnowski, T. J. Neurocomputational models of working memory. Nature Neurosci. 3, 1184–1191 (2000)

    Article  CAS  PubMed  Google Scholar 

  5. Compte, A., Sanchez-Vives, M. V., McCormick, D. A. & Wang, X. J. Cellular and network mechanisms of slow oscillatory activity (<1 Hz) in a cortical network model. J. Neurophysiol. 89, 2707–2725 (2003)

    Article  PubMed  Google Scholar 

  6. Fuster, J. M. Memory in the Cerebral Cortex (MIT press, Cambridge, Massachusetts, 1995)

    Google Scholar 

  7. Brunel, N. & Wang, X. J. Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition. J. Comput. Neurosci. 11, 63–85 (2001)

    Article  CAS  PubMed  Google Scholar 

  8. Hahnloser, R. H. R., Douglas, R. J. & Hepp, K. Attentional recruitment of inter-areal recurrent networks for selective gain control. Neural Comput. 14, 1669–1689 (2002)

    Article  PubMed  MATH  Google Scholar 

  9. Chance, F. S., Abbott, L. F. & Reyes, A. D. Gain modulation from background synaptic input. Neuron 35, 773–782 (2002)

    Article  CAS  PubMed  Google Scholar 

  10. Steriade, M., Nunez, A. & Amzica, F. A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J. Neurosci. 13, 3252–3265 (1993)

    Article  CAS  PubMed  Google Scholar 

  11. Contreras, D., Timofeev, I. & Steriade, M. Mechanisms of long lasting hyperpolarizations underlying slow sleep oscillations in cat corticothalamic networks. J. Physiol. (Lond.) 494, 251–264 (1996)

    Article  CAS  Google Scholar 

  12. Steriade, M., Timofeev, I. & Grenier, F. Natural waking and sleep states, a view from inside neocortical neurons. J. Neurophysiol. 85, 1969–1985 (2001)

    Article  CAS  PubMed  Google Scholar 

  13. Sanchez-Vives, M. V. & McCormick, D. A. Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nature Neurosci. 3, 1027–1034 (2000)

    Article  CAS  PubMed  Google Scholar 

  14. Cowan, R. L. & Wilson, C. J. Spontaneous firing patterns and axonal projections of single corticostriatal neurons in rat medial agranular cortex. J. Neurophysiol. 71, 17–32 (1994)

    Article  CAS  PubMed  Google Scholar 

  15. Egorov, A. V., Hamam, B. N., Fransen, E., Hasselmo, M. E. & Alonso, A. A. Graded persistent activity in entorhinal cortex neurons. Nature 420, 173–178 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  16. Compte, A. et al. Temporal fluctuations of mnemonic persistent activity in prefrontal neurons of monkeys during a delayed response task. J. Neurophysiol. (submitted)

  17. Funahashi, S., Bruce, C. J. & Goldman-Rakic, P. S. Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J. Neurophysiol. 61, 331–349 (1989)

    Article  CAS  PubMed  Google Scholar 

  18. Borg-Graham, L. J., Monier, C. & Frégnac, Y. Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 393, 369–372 (1998)

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Hirsch, J. A. & Gilbert, C. D. Synaptic physiology of horizontal connections in cat's visual cortex. J. Neurosci. 11, 1800–1809 (1991)

    Article  CAS  PubMed  Google Scholar 

  20. Anderson, J. S., Carandini, M. & Ferster, D. Orientation tuning of input conductance, excitation, and inhibition in cat primary visual cortex. J. Neurophysiol. 84, 909–926 (2000)

    Article  CAS  PubMed  Google Scholar 

  21. Hirsch, J. A., Alonso, J. M., Reid, R. C. & Martinez, L. M. Synaptic integration in striate cortical simple cells. J. Neurosci. 18, 9517–9528

  22. Carandini, M. & Heeger, D. J. Summation and division by neurons in primary visual cortex. Science 264, 1333–1336 (1994)

    Article  ADS  CAS  PubMed  Google Scholar 

  23. Gutkin, B. S., Laing, C. R., Colby, C. L., Show, C. C. & Ermentrout, G. B. Turning on and off with excitation: the role of spike-timing asynchrony and synchrony in sustained neural activity. J. Comput. Neurosci. 11, 121–134 (2001)

    Article  CAS  PubMed  Google Scholar 

  24. Mao, B. Q., Hamzei-Sichani, F., Aronov, D., Froemke, R. C. & Yuste, R. Dynamics of spontaneous activity in neocortical slices. Neuron 32, 883–898 (2001)

    Article  CAS  PubMed  Google Scholar 

  25. Cossart, R., Aronov, D. & Yuste, R. Attractor dynamics of network UP states in the neocortex. Nature 423, 283–288 (2003)

    Article  ADS  CAS  PubMed  Google Scholar 

  26. Bernander, Ö., Douglas, R. J., Martin, K. A. C. & Koch, C. Synaptic background activity influences spatiotemporal integration in single pyramidal cells. Proc. Natl Acad. Sci. USA 88, 11569–11573 (1991)

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Anderson, J. S., Lampl, I., Gillespie, D. C. & Ferster, D. The contribution of noise to contrast invariance of orientation tuning in cat visual cortex. Science 290, 1968–1972 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  28. Hahnloser, R. H., Sarpeshkar, R., Mahowald, M. A., Douglas, R. J. & Seung, H. S. Digital selection and analogue amplification coexist in a cortex-inspired silicon circuit. Nature 405, 947–951 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Stern, P., Edwards, F. A. & Sakmann, B. Fast and slow components of unitary EPSCs on stellate cells elicited by focal stimulation in slices of rat visual cortex. J. Physiol. (Lond.) 449, 247–278 (1992)

    Article  CAS  Google Scholar 

  30. Connors, B. W., Malenka, R. C. & Silva, L. R. Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat. J. Physiol. (Lond.) 406, 443–468 (1988)

    Article  CAS  Google Scholar 

Download references


We thank R. Yuste for his comments. This work was supported by the National Institutes of Health (D.A.M.), the Human Frontier Science Program (D.A.M.), and by a fellowship from the Howard Hughes Institute (A.H.).

Author information

Authors and Affiliations


Corresponding author

Correspondence to David A. McCormick.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shu, Y., Hasenstaub, A. & McCormick, D. Turning on and off recurrent balanced cortical activity. Nature 423, 288–293 (2003).

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


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