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:

Routing of spike series by dynamic circuits in the hippocampus

Abstract

Recurrent inhibitory loops are simple neuronal circuits found in the central nervous system, yet little is known about the physiological rules governing their activity. Here we use simultaneous somatic and dendritic recordings in rat hippocampal slices to show that during a series of action potentials in pyramidal cells recurrent inhibition rapidly shifts from their soma to the apical dendrites. Two distinct inhibitory circuits are sequentially recruited to produce this shift: one, time-locked with submillisecond precision to the onset of the action potential series, transiently inhibits the somatic and perisomatic regions of pyramidal cells; the other, activated in proportion to the rate of action potentials in the series, durably inhibits the distal apical dendrites. These two operating modes result from the synergy between pre- and postsynaptic properties of excitatory synapses onto recurrent inhibitory neurons with distinct projection patterns. Thus, the onset of a series of action potentials and the rate of action potentials in the series are selectively captured and transformed into different spatial patterns of recurrent inhibition.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Shift of recurrent inhibition along the somato-dendritic axis.
Figure 2: Transient activation of somatic and delayed activation of dendritic inhibitory conductances.
Figure 3: Onset-transient and late-persistent interneurons project to distinct layers.
Figure 4: Coincidence detection and integration in onset-transient versus late-persistent interneurons.
Figure 5: Disynaptic inhibition contributes to transience in onset-transient and to delay in late-persistent interneurons.

Similar content being viewed by others

References

  1. Adrian, E. D. The Basis of Sensation: The Action of the Sense Organs (W. W. Norton, New York, 1928)

    Google Scholar 

  2. Rieke, F., Warland, D., de Ruyter van Steveninck, R. & Bialek, W. Spikes: Exploring the Neural Code (The MIT Press, Cambridge, Massachusetts/London, UK, 1997)

    MATH  Google Scholar 

  3. Dayan, P. & Abbott, L. F. Theoretical Neurosciences: Computational and Mathematical Modeling of Neural Systems (The MIT Press, Cambridge, Massachusetts/London, UK, 2001)

    MATH  Google Scholar 

  4. Andersen, P., Eccles, J. C. & Loyning, Y. Recurrent inhibition in the hippocampus with identification of the inhibitory cell and its synapses. Nature 198, 540–542 (1963)

    Article  ADS  CAS  Google Scholar 

  5. Megias, M., Emri, Z., Freund, T. F. & Gulyas, A. I. Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells. Neuroscience 102, 527–540 (2001)

    Article  CAS  Google Scholar 

  6. Stuart, G. J., Dodt, H. U. & Sakmann, B. Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy. Pflugers Arch. 423, 511–518 (1993)

    Article  CAS  Google Scholar 

  7. Spruston, N., Schiller, Y., Stuart, G. & Sakmann, B. Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. Science 268, 297–300 (1995)

    Article  ADS  CAS  Google Scholar 

  8. Pouille, F. & Scanziani, M. Enforcement of temporal fidelity in pyramidal cells by somatic feed-forward inhibition. Science 293, 1159–1160 (2001)

    Article  CAS  Google Scholar 

  9. Kandel, E. R., Spencer, W. A. & Brinley, F. J. Electrophysiology of hippocampal neurons. I. Sequential invasion and synaptic organization. J. Neurophysiol. 24, 225–242 (1961)

    Article  CAS  Google Scholar 

  10. Dingledine, R. & Langmoen, I. A. Conductance changes and inhibitory actions of hippocampal recurrent IPSPs. Brain Res. 185, 277–287 (1980)

    Article  CAS  Google Scholar 

  11. Alger, B. E. & Nicoll, R. A. Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro. J. Physiol. 328, 105–123 (1982)

    Article  CAS  Google Scholar 

  12. Maccaferri, G. & McBain, C. J. Passive propagation of LTD to stratum oriens-alveus inhibitory neurons modulates the temporoammonic input to the hippocampal CA1 region. Neuron 15, 137–145 (1995)

    Article  CAS  Google Scholar 

  13. Pearce, R. A. Physiological evidence for two distinct GABAA responses in rat hippocampus. Neuron 10, 189–200 (1993)

    Article  CAS  Google Scholar 

  14. Spruston, N., Jaffe, D. B., Williams, S. H. & Johnston, D. Voltage- and space-clamp errors associated with the measurement of electrotonically remote synaptic events. J. Neurophysiol. 70, 781–802 (1993)

    Article  CAS  Google Scholar 

  15. Freund, T. F. & Buzsáki, G. Interneurons of the hippocampus. Hippocampus 6, 347–470 (1996)

    Article  CAS  Google Scholar 

  16. Geiger, J. R. P., Lubke, J., Roth, A., Frotscher, M. & Jonas, P. Submillisecond AMPA receptor-mediated signaling at a principal neuron-interneuron synapse. Neuron 18, 1009–1023 (1997)

    Article  CAS  Google Scholar 

  17. Fricker, D. & Miles, R. EPSP amplification and the precision of spike timing in hippocampal neurons. Neuron 28, 559–569 (2000)

    Article  CAS  Google Scholar 

  18. Ali, A. B. & Thomson, A. M. Facilitating pyramid to horizontal oriens-alveus interneurone inputs: dual intracellular recordings in slices of rat hippocampus. J. Physiol. 507.1, 185–199 (1998)

    Article  Google Scholar 

  19. Ali, A. B., Deuchars, J., Pawelzik, H. & Thomson, A. M. CA1 pyramidal to basket and bistratified cell EPSPs: dual intracellular recordings in rat hippocampal slices. J. Physiol. 507.1, 201–219 (1998)

    Article  Google Scholar 

  20. Shigemoto, R. et al. Target-cell-specific concentration of a metabotropic glutamate receptor in the presynaptic active zone. Nature 381, 523–525 (1996)

    Article  ADS  CAS  Google Scholar 

  21. Scanziani, M., Gahwiler, B. H. & Charpak, S. Target cell-specific modulation of transmitter release at terminals from a single axon. Proc. Natl Acad. Sci. USA 95, 12004–12009 (1998)

    Article  ADS  CAS  Google Scholar 

  22. Toth, K., Suares, G., Lawrence, J. J., Philips-Tansey, E. & McBain, C. J. Differential mechanisms of transmission at three types of mossy fiber synapse. J. Neurosci. 20, 8279–8289 (2000)

    Article  CAS  Google Scholar 

  23. Losonczy, A., Zhang, L., Shigemoto, R., Somogyi, P. & Nusser, Z. Cell type dependence and variability in the short-term plasticity of EPSCs in identified mouse hippocampal interneurones. J. Physiol. 542, 193–210 (2002)

    Article  CAS  Google Scholar 

  24. Buhl, E. H., Szilagyi, T., Halasy, K. & Somogyi, P. Physiological properties of anatomically identified basket and bistratified cells in the CA1 area of the rat hippocampus in vitro. Hippocampus 6, 294–305 (1996)

    Article  CAS  Google Scholar 

  25. Gulyás, A. I., Megias, M., Emri, Z. & Freund, T. F. Total number and ratio of excitatory and inhibitory synapses converging onto single interneurons of different types in the CA1 area of the rat hippocampus. J. Neurosci. 19, 10082–10097 (1999)

    Article  Google Scholar 

  26. Banks, M. I., White, J. A. & Pearce, R. A. Interactions between distinct GABA(A) circuits in hippocampus. Neuron 25, 449–457 (2000)

    Article  CAS  Google Scholar 

  27. Arai, A. C., Xia, Y.-F., Rogers, G., Lynch, G. & Kessler, M. Benzamide-type AMPA receptor modulators form two subfamilies with distinct modes of action. J. Pharmacol. Exp. Ther. 303, 1075–1085 (2002)

    Article  CAS  Google Scholar 

  28. Klausberger, T. et al. Brain-state- and cell-type-specific firing of hippocampal interneurons in vivo. Nature 421, 844–849 (2003)

    Article  ADS  CAS  Google Scholar 

  29. O'Keefe, J. & Recce, M. L. Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3, 317–330 (1993)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  31. Beierlein, M., Gibson, J. R. & Connors, B. W. Two dynamically distinct inhibitory networks in layer 4 of the neocortex. J. Neurophysiol. 90, 2987–3000 (2003)

    Article  Google Scholar 

Download references

Acknowledgements

We thank B. Gähwiler from the Brain Research Institute of the University of Zürich, where the initial part of the study was performed. We thank J. Anderson for instructions on the use of the camera lucida. We also thank U. Gerber and M. Carandini for critical reading of and L. Glickfeld for comments on the manuscript. This work was supported by the Swiss National Science Foundation and NIH grants.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Massimo Scanziani.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Methods

Experimental protocols used to test the specificity of Alveus stimulation and to recover the morphology of recorded interneurons. (DOC 21 kb)

Supplementary Figure 1

Recurrent IPSPs are not contaminated by feed-forward IPSPs. (PDF 49 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pouille, F., Scanziani, M. Routing of spike series by dynamic circuits in the hippocampus. Nature 429, 717–723 (2004). https://doi.org/10.1038/nature02615

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature02615

This article is cited by

Comments

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.

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