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Determinants of different deep and superficial CA1 pyramidal cell dynamics during sharp-wave ripples

Nature Neuroscience 18, 1281–1290 (2015) | Download Citation

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Abstract

Sharp-wave ripples represent a prominent synchronous activity pattern in the mammalian hippocampus during sleep and immobility. GABAergic interneuronal types are silenced or fire during these events, but the mechanism of pyramidal cell (PC) participation remains elusive. We found opposite membrane polarization of deep (closer to stratum oriens) and superficial (closer to stratum radiatum) rat CA1 PCs during sharp-wave ripples. Using sharp and multi-site recordings in combination with neurochemical profiling, we observed a predominant inhibitory drive of deep calbindin (CB)-immunonegative PCs that contrasts with a prominent depolarization of superficial CB-immunopositive PCs. Biased contribution of perisomatic GABAergic inputs, together with suppression of CA2 PCs, may explain the selection of CA1 PCs during sharp-wave ripples. A deep-superficial gradient interacted with behavioral and spatial effects to determine cell participation during sleep and awake sharp-wave ripples in freely moving rats. Thus, the firing dynamics of hippocampal PCs are exquisitely controlled at subcellular and microcircuit levels in a cell type–selective manner.

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Acknowledgements

We thank P. Somogyi for his valuable guidance and suggestions on histological procedures and analyses. For gephyrin counting, B. Micklem advised on stereological approaches and K. Wagner helped with tissue processing. We thank B. Gal for histological processing for immunofluorescence studies and F. Laurent for suggestions for analysis. R. Miles, A. Gulyás and A. Colino provided useful comments and discussion. We also thank G. Tamás and V. Szemenyei for their generous support. This work was supported by a grant from the Spanish Ministerio de Economía y Competitividad (BFU2012-37156-C03-01). E.C. receives funding from the CSIC JAE Program, co-funded by the European Social Fund. M.V. was supported by the Spanish Ministry of Education, Culture and Sports (FPU12/03776) and by a short-term grant to visit the MRC Anatomical Neuropharmacological Unit in Oxford (FPU-EST13/01046). A.S.-A. is funded by the Universidad Complutense de Madrid. T.J.V. was supported by the UK Medical Research Council. R.G.A. was supported by an ERC Advanced grant (INTERIMPACT) to G. Tamás. D.G.-D. is funded by the Spanish Ministerio de Economía y Competitividad (BES-2013-064171).

Author information

    • Manuel Valero
    • , Elena Cid
    •  & Robert G Averkin

    These authors contributed equally to this work.

Affiliations

  1. Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.

    • Manuel Valero
    • , Elena Cid
    • , Alberto Sanchez-Aguilera
    • , Daniel Gomez-Dominguez
    • , Elisa Bellistri
    •  & Liset Menendez de la Prida

  2. Hungarian Academy of Sciences, University of Szeged Research Group for Cortical Microcircuits, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Szeged, Hungary.

    • Robert G Averkin

  3. Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla-La Mancha, Toledo, Spain.

    • Juan Aguilar

  4. Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, Madrid, Spain.

    • Alberto Sanchez-Aguilera

  5. Medical Research Council Brain Network Dynamics Unit, Department of Pharmacology, University of Oxford, Oxford, UK.

    • Tim J Viney

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Contributions

J.A. and L.M.d.l.P. first observed the phenomenon. L.M.d.l.P. designed and coordinated the study. M.V., J.A. and L.M.d.l.P. obtained in vivo sharp recordings. A.S.-A. and L.M.d.l.P. performed in vitro experiments. M.V. and R.G.A. obtained recordings from freely moving rats. E.C. was responsible for the immunohistological characterization of recorded cells. M.V. and T.J.V. were responsible for identification and quantification of perisomatic GABAergic boutons. M.V., E.C., A.S.-A., T.J.V., E.B., D.G.-D. and L.M.d.l.P. analyzed and interpreted the data. L.M.P. wrote the paper. J.A. and A.S.-A. contributed equally to this work.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Liset Menendez de la Prida.

Integrated supplementary information

Supplementary figures

  1. 1.

    Methodological approaches and pharmacological manipulations in vivo

  2. 2.

    Relationship between SPW sinks and sources and the intracellular membrane potential

  3. 3.

    Analysis of intracellular and extracellular ripple oscillations

  4. 4.

    Measurement of calbindin immunoreactivity on intracellular recorded cells

  5. 5.

    Lack of gephyrin immunoreactivity in recorded pyramidal neurons.

  6. 6.

    In vitro analysis of synaptic currents in deep and superficial CA1 pyramidal cells

  7. 7.

    Single-cell recordings in drug-free freely moving conditions and definition of behavioral states.

  8. 8.

    Microcircuit mechanisms controlling heterogeneous CA1 behavior during SPW-ripple events

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    Supplementary Text and Figures

    Supplementary Figures 1–8 and Supplementary Tables 1 and 2

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DOI

https://doi.org/10.1038/nn.4074

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