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A computer model of unitary responses from associational/commissural and perforant path synapses in hippocampal CA3 pyramidal cells

Journal of Computational Neuroscience volume 31, pages 137–158 (2011)Cite this article

An Erratum to this article was published on 12 October 2011

Abstract

Despite the central position of CA3 pyramidal cells in the hippocampal circuit, the experimental investigation of their synaptic properties has been limited. Recent slice experiments from adult rats characterized AMPA and NMDA receptor unitary synaptic responses in CA3b pyramidal cells. Here, excitatory synaptic activation is modeled to infer biophysical parameters, aid analysis interpretation, explore mechanisms, and formulate predictions by contrasting simulated somatic recordings with experimental data. Reconstructed CA3b pyramidal cells from the public repository NeuroMorpho.Org were used to allow for cell-specific morphological variation. For each cell, synaptic responses were simulated for perforant pathway and associational/commissural synapses. Means and variability for peak amplitude, time-to-peak, and half-height width in these responses were compared with equivalent statistics from experimental recordings. Synaptic responses mediated by AMPA receptors are best fit with properties typical of previously characterized glutamatergic receptors where perforant path synapses have conductances twice that of associational/commissural synapses (0.9 vs. 0.5 nS) and more rapid peak times (1.0 vs. 3.3 ms). Reanalysis of passive-cell experimental traces using the model shows no evidence of a CA1-like increase of associational/commissural AMPA receptor conductance with increasing distance from the soma. Synaptic responses mediated by NMDA receptors are best fit with rapid kinetics, suggestive of NR2A subunits as expected in mature animals. Predictions were made for passive-cell current clamp recordings, combined AMPA and NMDA receptor responses, and local dendritic depolarization in response to unitary stimulations. Models of synaptic responses in active cells suggest altered axial resistivity and the presence of synaptically activated potassium channels in spines.

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Grants

This work was supported by National Institutes of Health grants AG025633 and NS39600.

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Author notes

  1. Tamara Perez-Rosello & Michele Migliore

    Present address: Institute of Biophysics, National Research Council, Palermo, Italy

Affiliations

  1. Center for Neural Informatics, Structures, & Plasticity, George Mason University, 4400 University Drive, MS 2A1, Fairfax, VA, 22030, USA

    John L. Baker, Michele Migliore & Giorgio A. Ascoli

  2. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA

    Tamara Perez-Rosello & Germán Barrionuevo

  3. Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Tamara Perez-Rosello

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  1. John L. Baker
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  2. Tamara Perez-Rosello
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  5. Giorgio A. Ascoli
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Correspondence to Giorgio A. Ascoli.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10827-011-0364-6

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Baker, J.L., Perez-Rosello, T., Migliore, M. et al. A computer model of unitary responses from associational/commissural and perforant path synapses in hippocampal CA3 pyramidal cells. J Comput Neurosci 31, 137–158 (2011). https://doi.org/10.1007/s10827-010-0304-x

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Keywords

  • AMPA receptor
  • NMDA receptor
  • Hippocampus