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Examining the limits of cellular adaptation bursting mechanisms in biologically-based excitatory networks of the hippocampus

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Abstract

Determining the biological details and mechanisms that are essential for the generation of population rhythms in the mammalian brain is a challenging problem. This problem cannot be addressed either by experimental or computational studies in isolation. Here we show that computational models that are carefully linked with experiment provide insight into this problem. Using the experimental context of a whole hippocampus preparation in vitro that spontaneously expresses theta frequency (3–12 Hz) population bursts in the CA1 region, we create excitatory network models to examine whether cellular adaptation bursting mechanisms could critically contribute to the generation of this rhythm. We use biologically-based cellular models of CA1 pyramidal cells and network sizes and connectivities that correspond to the experimental context. By expanding our mean field analyses to networks with heterogeneity and non all-to-all coupling, we allow closer correspondence with experiment, and use these analyses to greatly extend the range of parameter values that are explored. We find that our model excitatory networks can produce theta frequency population bursts in a robust fashion.Thus, even though our networks are limited by not including inhibition at present, our results indicate that cellular adaptation in pyramidal cells could be an important aspect for the occurrence of theta frequency population bursting in the hippocampus. These models serve as a starting framework for the inclusion of inhibitory cells and for the consideration of additional experimental features not captured in our present network models.

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Conflict of interests

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Fundamental Neurobiology, Toronto Western Research Institute (TWRI), University Health Network (UHN), Krembil Discovery Tower (KDT), 60 Leonard Ave. 7KD411, Toronto, Ontario, M5T 2S8, Canada

    K. A. Ferguson, F. Njap & F. K. Skinner

  2. Department of Physiology, University of Toronto, Toronto, Ontario, Canada

    K. A. Ferguson

  3. Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, N2L 3G1, Canada

    F. Njap, W. Nicola & S. A. Campbell

  4. Departments of Medicine (Neurology) and Physiology, University of Toronto, Toronto, Ontario, Canada

    F. K. Skinner

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  1. K. A. Ferguson
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  2. F. Njap
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  3. W. Nicola
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  4. F. K. Skinner
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  5. S. A. Campbell
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Corresponding authors

Correspondence to F. K. Skinner or S. A. Campbell.

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Action Editor: David Terman

This work was supported by NSERC Canada.

K. A. Ferguson, F. Njap and W. Nicola are Shared First Authors

F. K. Skinner and S. A. Campbell are Shared Senior Authors

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Ferguson, K.A., Njap, F., Nicola, W. et al. Examining the limits of cellular adaptation bursting mechanisms in biologically-based excitatory networks of the hippocampus. J Comput Neurosci 39, 289–309 (2015). https://doi.org/10.1007/s10827-015-0577-1

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  • DOI: https://doi.org/10.1007/s10827-015-0577-1

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