A computer model of unitary responses from associational/commissural and perforant path synapses in hippocampal CA3 pyramidal cells
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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.
KeywordsAMPA receptor NMDA receptor Hippocampus
This work was supported by National Institutes of Health grants AG025633 and NS39600.
- Carnevale, N. T., & Hines, M. L. (2005). The NEURON book. New York: Cambridge University Press.Google Scholar
- Colquhoun, D., Jonas, P., & Sakmann, B. (1992). Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices. Journal de Physiologie, 458, 261–287.Google Scholar
- Dayan, P., & Abbott, L. (2001). Theoretical neuroscience. Cambridge: MIT.Google Scholar
- Destexhe, A., Mainen, Z. F., & Sejnowski, T. J. (1998). Kinetic models of synaptic transmission. In C. Koch & I. Segev (Eds.), Methods in neuronal modeling: From ions to networks (2nd ed., pp. 1–15). Cambridge: MIT.Google Scholar
- Feldmeyer, D., Lübke, J., Silver, R. A., & Sakmann, B. (2002). Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column. Journal de Physiologie, 538, 803–822.CrossRefGoogle Scholar
- Iansek, R., & Redman, S. J. (1973). The amplitude, time course, and charge of unitary excitatory post-synaptic potentials evoked in spinal motoneurone dendrites. Journal de Physiologie, 234, 665–688.Google Scholar
- Jonas, P., & Sakmann, B. (1992). Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices. Journal de Physiologie, 455, 143–171.Google Scholar
- Jonas, P., Major, G., & Sakmann, B. (1993). Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus. Journal de Physiologie, 472, 615–663.Google Scholar
- Miles, R., & Wong, R. K. S. (1986). Excitatory synaptic interactions between CA3 neurones in the guinea-pig hippocampus. Journal de Physiologie, 373, 397–418.Google Scholar
- Miller, R. G., Jr. (1998). Beyond ANOVA: Basics of applied statistics. New York: Chapman & Hall/CRC.Google Scholar
- Perez-Rosello, T., Baker, J. L., Ferrante, M., Iyengar, S., Ascoli, G. A., Barrionuevo, G. (2010). Passive and active shaping of unitary responses from associational/commissural and perforant path synapses in hippocampal CA3 pyramidal cells. Journal of Computational Neuroscience (in press).Google Scholar
- R Development Core Team (2009). R: A language and environment for statistical computing [Online]. R Foundation for Statistical Computing. http://www.R-project.org. Accessed October 19, 2009.
- Ramón y Cajal, S. (1995). Histology of the nervous system of man and vertebrates. Translation from the French edition by Swanson N, Swanson LW. New York: Oxford University Press.Google Scholar
- Spruston, N., Jonas, P., & Sakmann, B. (1995). Dendritic glutamate receptor channels in rat hippocampal CA3 and CA1 pyramidal neurons. Journal de Physiologie, 482, 325–352.Google Scholar