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Cannabinoids reveal importance of spike timing coordination in hippocampal function

Nature Neuroscience 9, 1526–1533 (2006) | Download Citation

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Abstract

Cannabinoids impair hippocampus-dependent memory in both humans and animals, but the network mechanisms responsible for this effect are unknown. Here we show that the cannabinoids Δ9-tetrahydrocannabinol and CP55940 decreased the power of theta, gamma and ripple oscillations in the hippocampus of head-restrained and freely moving rats. These effects were blocked by a CB1 antagonist. The decrease in theta power correlated with memory impairment in a hippocampus-dependent task. By simultaneously recording from large populations of single units, we found that CP55940 severely disrupted the temporal coordination of cell assemblies in short time windows (<100 ms) yet only marginally affected population firing rates of pyramidal cells and interneurons. The decreased power of local field potential oscillations correlated with reduced temporal synchrony but not with firing rate changes. We hypothesize that reduced spike timing coordination and the associated impairment of physiological oscillations are responsible for cannabinoid-induced memory deficits.

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Acknowledgements

We thank C. Geisler, K.D. Harris, H. Hirase, A. Sirota and M. Zugaro for their help with data analysis and A. Amarasingham, S.A. Deadwyler, K. Diba and O.J. Manzoni for comments on earlier versions of this manuscript. Supported by grants from the NIH (G.B.: NS34994, NS43157, MH54671; B.L.M.: NS20331) and the Human Science Program Organization and the European Molecular Biology Organization (D.R.).

Author information

Affiliations

  1. Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, USA.

    • David Robbe
    • , Sean M Montgomery
    • , Pavel E Rueda-Orozco
    •  & György Buzsaki

  2. Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, Arizona 85724, USA.

    • Alexander Thome
    •  & Bruce L McNaughton

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Contributions

D.R. conducted the recordings in head-restrained, anesthetized and freely moving (n= 3) rats and did most of the data analysis. S.M.M. conducted recordings in freely moving rats (n= 2) and designed the covariance analysis test. P.E.R.-O. participated in the recordings of two freely moving rats. A.T. conducted and B.L.M. supervised the Δ9-THC experiments. G.B. supervised the project and cowrote the manuscript with D.R. and S.M.M.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to György Buzsaki.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    The CB1 receptor antagonist SR141716A (1.5 mg kg−1) did not significantly affect network properties or firing patterns of single neurons.

  2. 2.

    Supplementary Fig. 2

    Parallel recording and clustering of unit activity in the CA1 pyramidal layer by an 8-shank, 64-site silicon probe.

  3. 3.

    Supplementary Fig. 3

    Effect of CP55940 on interspike intervals distribution (ISI) of hippocampal CA1 cells.

  4. 4.

    Supplementary Fig. 4

    Cannabinoid-induced alteration of firing patterns of hippocampal cells.

  5. 5.

    Supplementary Methods

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DOI

https://doi.org/10.1038/nn1801

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