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.

Oscillatory dynamics in the hippocampus support dentate gyrus–CA3 coupling


Gamma oscillations in the dentate gyrus and hippocampal CA3 show variable coherence in vivo, but the mechanisms and relevance for information flow are unknown. We found that carbachol-induced oscillations in rat CA3 have biphasic phase-response curves, consistent with the ability to couple with oscillations in afferent projections. Differences in response to stimulation of either the intrinsic feedback circuit or the dentate gyrus were well described by varying an impulse vector in a two-dimensional dynamical system, representing the relative input to excitatory and inhibitory neurons. Responses to sinusoidally modulated optogenetic stimulation confirmed that the CA3 network oscillation can entrain to periodic inputs, with a steep dependence of entrainment phase on input frequency. CA3 oscillations are therefore suited to coupling with oscillations in the dentate gyrus over a broad range of frequencies.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Measurement of network PRCs in the hippocampal CA3 subfield.
Figure 2: A neural mass model reproduces rephasing behavior.
Figure 3: Population data and model behavior.
Figure 4
Figure 5: Optogenetic rephasing.
Figure 6: Entrainment demonstrated with modulated light ramps.


  1. Bragin, A. et al. Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat. J. Neurosci. 15, 47–60 (1995).

    Article  CAS  Google Scholar 

  2. Csicsvari, J., Jamieson, B., Wise, K.D. & Buzsaki, G. Mechanisms of gamma oscillations in the hippocampus of the behaving rat. Neuron 37, 311–322 (2003).

    Article  CAS  Google Scholar 

  3. Montgomery, S.M., Sirota, A. & Buzsáki, G. Theta and gamma coordination of hippocampal networks during waking and rapid eye movement sleep. J. Neurosci. 28, 6731–6741 (2008).

    Article  CAS  Google Scholar 

  4. Montgomery, S.M. & Buzsaki, G. Gamma oscillations dynamically couple hippocampal CA3 and CA1 regions during memory task performance. Proc. Natl. Acad. Sci. USA 104, 14495–14500 (2007).

    Article  CAS  Google Scholar 

  5. Fell, J. et al. Human memory formation is accompanied by rhinal-hippocampal coupling and decoupling. Nat. Neurosci. 4, 1259–1264 (2001).

    Article  CAS  Google Scholar 

  6. Salinas, E. & Sejnowski, T.J. Correlated neuronal activity and the flow of neural information. Nat. Rev. Neurosci. 2, 539–550 (2001).

    Article  CAS  Google Scholar 

  7. Fries, P. A mechanism for cognitive dynamics: neuronal communication through neuronal coherence. Trends Cogn. Sci. 9, 474–480 (2005).

    Article  Google Scholar 

  8. Akam, T. & Kullmann, D. Oscillations and filtering networks support flexible routing of information. Neuron 67, 308–320 (2010).

    Article  CAS  Google Scholar 

  9. Hájos, N. et al. Spike timing of distinct types of GABAergic interneuron during hippocampal gamma oscillations in vitro. J. Neurosci. 24, 9127–9137 (2004).

    Article  Google Scholar 

  10. Hasenstaub, A. et al. Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks. Neuron 47, 423–435 (2005).

    Article  CAS  Google Scholar 

  11. Mann, E.O., Suckling, J.M., Hajos, N., Greenfield, S.A. & Paulsen, O. Perisomatic feedback inhibition underlies cholinergically induced fast network oscillations in the rat hippocampus in vitro. Neuron 45, 105–117 (2005).

    Article  CAS  Google Scholar 

  12. Hansel, D., Mato, G. & Meunier, C. Synchrony in excitatory neural networks. Neural Comput. 7, 307–337 (1995).

    Article  CAS  Google Scholar 

  13. Smeal, R.M., Ermentrout, G.B. & White, J.A. Phase-response curves and synchronized neural networks. Philos. Trans. R. Soc. Lond. B Biol. Sci. 365, 2407 (2010).

    Article  Google Scholar 

  14. Izhikevich, E.M. Dynamical Systems in Neuroscience: the Geometry of Excitability and Bursting 443–505 (MIT Press, Cambridge, Massachusetts, USA, 2006).

  15. Brunel, N. & Hakim, V. Sparsely synchronized neuronal oscillations. Chaos 18, 015113 (2008).

    Article  Google Scholar 

  16. Oren, I., Mann, E.O., Paulsen, O. & Hajos, N. Synaptic currents in anatomically identified CA3 neurons during hippocampal gamma oscillations in vitro. J. Neurosci. 26, 9923–9934 (2006).

    Article  CAS  Google Scholar 

  17. Wilson, H.R. & Cowan, J.D. Excitatory and inhibitory interactions in localized populations of model neurons. Biophys. J. 12, 1–24 (1972).

    Article  CAS  Google Scholar 

  18. Winfree, A. The Geometry of Biological Time 2nd edn. (Springer-Verlag, New York, 2000).

  19. Acsády, L., Kamondi, A., Sik, A., Freund, T. & Buzsáki, G. GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. J. Neurosci. 18, 3386–3403 (1998).

    Article  Google Scholar 

  20. Mori, M., Abegg, M.H., Gahwiler, B.H. & Gerber, U. A frequency-dependent switch from inhibition to excitation in a hippocampal unitary circuit. Nature 431, 453–456 (2004).

    Article  CAS  Google Scholar 

  21. Adesnik, H. & Scanziani, M. Lateral competition for cortical space by layer-specific horizontal circuits. Nature 464, 1155–1160 (2010).

    Article  CAS  Google Scholar 

  22. Pálhalmi, J., Paulsen, O., Freund, T.F. & Hájos, N. Distinct properties of carbachol- and DHPG-induced network oscillations in hippocampal slices. Neuropharmacology 47, 381–389 (2004).

    Article  Google Scholar 

  23. Coombes, S. Large-scale neural dynamics: simple and complex. Neuroimage 52, 731–739 (2010).

    Article  CAS  Google Scholar 

  24. Ermentrout, B. Type I membranes, phase resetting curves and synchrony. Neural Comput. 8, 979–1001 (1996).

    Article  CAS  Google Scholar 

  25. Brunel, N. & Hakim, V. Fast global oscillations in networks of integrate-and-fire neurons with low firing rates. Neural Comput. 11, 1621–1671 (1999).

    Article  CAS  Google Scholar 

  26. Brunel, N. Dynamics of sparsely connected networks of excitatory and inhibitory spiking neurons. J. Comput. Neurosci. 8, 183–208 (2000).

    Article  CAS  Google Scholar 

  27. Atallah, B.V. & Scanziani, M. Instantaneous modulation of gamma oscillation frequency by balancing excitation with inhibition. Neuron 62, 566–577 (2009).

    Article  CAS  Google Scholar 

  28. Cardin, J.A. et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459, 663–667 (2009).

    Article  CAS  Google Scholar 

  29. Fisher, N.I. & Lewis, T. Estimating the common mean direction of several circular or spherical distributions with differing dispersions. Biometrika 70, 333 (1983).

    Article  Google Scholar 

  30. Fisher, N.I. & Lee, A.K. A correlation coefficient for circular data. Biometrika 70, 327–332 (1983).

    Article  Google Scholar 

  31. Rinzel, J. & Ermentrout, G.B. Analysis of neural excitability and oscillations. in Methods in Neuronal Modeling: From Ions to Networks 2nd edn. (eds. Koch, C. & Segev, I.) 251–292 (MIT Press, Cambridge, MA, USA, 1998).

  32. Latham, P.E., Richmond, B.J., Nelson, P.G. & Nirenberg, S. Intrinsic dynamics in neuronal networks. I. Theory. J. Neurophysiol. 83, 808–827 (2000).

    Article  CAS  Google Scholar 

Download references


We are grateful to N. Burgess for comments on the manuscript and to K. Deisseroth for the ChR2 plasmid. This work was supported by the Wellcome Trust, the European Research Council, the Brain Research Trust and the Guarantors of Brain.

Author information

Authors and Affiliations



T.A. and D.M.K. designed the experiments and wrote the manuscript. T.A. and E.F. conducted the electrical stimulation rephasing experiments. I.O. conducted the intracellular recording experiments. T.A. and L.M. conducted the optogenetic experiments. T.A. performed the computational modeling and data analysis.

Corresponding authors

Correspondence to Thomas Akam or Dimitri M Kullmann.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–4 (PDF 2679 kb)

Supplementary Video 1a

Rephasing Animations: Weak alveus stimulation (MOV 2747 kb)

Supplementary Video 1b

Rephasing Animations: Strong alveus stimulation (MOV 2554 kb)

Supplementary Video 1c

Rephasing Animations: Weak dentate stimulation (MOV 2748 kb)

Supplementary Video 1d

Rephasing Animations: Weak dentate stimulation (MOV 2393 kb)

Supplementary Video 2a

Intracellular current trajectory animations: alveus stimulation (MOV 459 kb)

Supplementary Video 2b

Intracellular current trajectory animations: dentate stimulation (MOV 1503 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Akam, T., Oren, I., Mantoan, L. et al. Oscillatory dynamics in the hippocampus support dentate gyrus–CA3 coupling. Nat Neurosci 15, 763–768 (2012).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


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