[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content
Springer Nature Link
Log in

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

  • Published:
Journal of Computational Neuroscience Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  • Amaral, D. G., Ishizuka, N., & Claiborne, B. (1990). Neurons, numbers and the hippocampal network. Progress in Brain Research, 83, 1–11.

    Article  PubMed  CAS  Google Scholar 

  • Amaral, D. G., & Witter, M. P. (1989). The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience, 31, 571–591.

    Article  PubMed  CAS  Google Scholar 

  • Andrásfalvy, B. K., & Magee, J. C. (2001). Distance-dependent increase in AMPA receptor number in the dendrites of adult hippocampal CA1 pyramidal neurons. The Journal of Neuroscience, 21, 9151–9159.

    PubMed  Google Scholar 

  • Ascoli, G. A., Donohue, D. E., & Halavi, M. (2007). NeuroMorpho.Org: a central resource for neuronal morphologies. Journal of Neuroscience, 27, 9247–9251.

    Article  PubMed  CAS  Google Scholar 

  • Baker, J. L., & Olds, J. L. (2007). Theta phase precession emerges from a hybrid computational model of a CA3 place cell. Cognitive Neurodynamics, 1, 237–248.

    Article  PubMed  Google Scholar 

  • Bekkers, J. M., & Stevens, C. F. (1996). Cable properties of cultured hippocampal neurons determined from sucrose-evoked miniature EPSCs. Journal of Neurophysiology, 75, 1250–1255.

    PubMed  CAS  Google Scholar 

  • Berzhanskaya, J., Urban, N. N., & Barrionuevo, G. (1998). Electrophysiological and pharmacological characterization of the direct perforant path input to hippocampal area CA3. Journal of Neurophysiology, 79, 2111–2118.

    PubMed  CAS  Google Scholar 

  • Bloodgood, B. L., & Sabatini, B. L. (2007). Nonlinear regulation of unitary synaptic signals by CaV2.3 voltage-sensitive calcium channels located in dendritic spines. Neuron, 53, 249–260.

    Article  PubMed  CAS  Google Scholar 

  • Cais, O., Sedlacek, M., Horak, M., Dittert, I., & Vyklicky, L., Jr. (2008). Temperature dependence of NR1/NR2B NMDA receptor channels. Neuroscience, 151, 428–438.

    Article  PubMed  CAS  Google Scholar 

  • Carnevale, N. T., & Hines, M. L. (2005). The NEURON book. New York: Cambridge University Press.

    Google Scholar 

  • Chen, N., Ren, J., Raymond, L. A., & Murphy, T. H. (2001). Changes in agonist concentration dependence that are a function of duration of exposure suggest N-methyl-d-aspartate receptor nonsaturation during synaptic stimulation. Molecular Pharmacology, 59, 212–219.

    PubMed  CAS  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.

    CAS  Google Scholar 

  • Cull-Candy, S., Brickley, S., & Farrant, M. (2001). NMDA receptor subunits: diversity, development and disease. Current Opinion in Neurobiology, 11, 327–335.

    Article  PubMed  CAS  Google Scholar 

  • Dalby, N. O., & Mody, I. (2003). Activation of NMDA receptors in rat dentate gyrus granule cells by spontaneous and evoked transmitter release. Journal of Neurophysiology, 90, 786–797.

    Article  PubMed  CAS  Google Scholar 

  • Dayan, P., & Abbott, L. (2001). Theoretical neuroscience. Cambridge: MIT.

    Google Scholar 

  • Debanne, D., Guérineau, N. C., Gähwiler, B. H., & Thompson, S. M. (1995). Physiology and pharmacology of unitary synaptic connections between pairs of cells in areas CA3 and CA1 of rat hippocampal slice cultures. Journal of Neurophysiology, 73, 1282–1294.

    PubMed  CAS  Google Scholar 

  • Debanne, D., Gähwiler, B. H., & Thompson, S. M. (1998). Long-term synaptic plasticity between pairs of individual CA3 pyramidal cells in rat hippocampal slice cultures. Journal de Physiologie, 507, 237–247.

    Article  CAS  Google Scholar 

  • Debanne, D., Gähwiler, B. H., & Thompson, S. M. (1999). Heterogeneity of synaptic plasticity at unitary CA3-CA1 and CA3-CA3 connections in rat hippocampal slice cultures. The Journal of Neuroscience, 19, 10664–10671.

    PubMed  CAS  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 

  • Diamond, J. S. (2001). Neuronal glutamate transporters limit activation of NMDA receptors by neurotransmitter spillover on CA1 pyramidal cells. The Journal of Neuroscience, 21, 8328–8338.

    PubMed  CAS  Google Scholar 

  • Do, V. H., Martinez, C. O., Martinez, J. L., Jr., & Derrick, B. E. (2002). Long-term potentiation in direct perforant path projections to the hippocampal CA3 region in vivo. Journal of Neurophysiology, 87, 669–678.

    PubMed  Google Scholar 

  • Erreger, K., Dravid, S. M., Banke, T. G., Wyllie, D. J. A., & Traynelis, S. F. (2005). Subunit-specific gating controls rat NR1/NR2A and NR1/NR2B NMDA channel kinetics and synaptic signalling profiles. Journal de Physiologie, 563, 345–358.

    Article  CAS  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.

    Article  CAS  Google Scholar 

  • Geiger, J. R., Lübke, J., Roth, A., Frotscher, M., & Jonas, P. (1997). Submillisecond AMPA receptor-mediated signaling at a principal neuron-interneuron synapse. Neuron, 18, 1009–1023.

    Article  PubMed  CAS  Google Scholar 

  • Gentet, L. J., Stuart, G. J., & Clements, J. D. (2000). Direct measurement of specific membrane capacitance in neurons. Biophysical Journal, 79, 314–320.

    Article  PubMed  CAS  Google Scholar 

  • Golding, N. L., Mickus, T. J., Katz, Y., Kath, W. L., & Spruston, N. (2005). Factors mediating powerful voltage attenuation along CA1 pyramidal neuron dendrites. Journal de Physiologie, 568, 69–82.

    Article  CAS  Google Scholar 

  • Hemond, P., Epstein, D., Boley, A., Migliore, M., Ascoli, G. A., & Jaffe, D. B. (2008). Distinct classes of pyramidal cells exhibit mutually exclusive firing patterns in hippocampal area CA3b. Hippocampus, 18, 411–424.

    Article  PubMed  Google Scholar 

  • Hemond, P., Migliore, M., Ascoli, G. A., & Jaffe, D. B. (2009). The membrane response of CA3b pyramidal neurons near rest: heterogeneity of passive properties and the contribution of hyperpolarization-activated currents. Neuroscience, 160, 359–370.

    Article  PubMed  CAS  Google Scholar 

  • Henze, D., Cameron, W. E., & Barrionuevo, G. (1996). Dendritic morphology and its effects on the amplitude and rise-time of synaptic signals in hippocampal CA3 pyramidal cells. The Journal of Comparative Neurology, 369, 331–344.

    Article  PubMed  CAS  Google Scholar 

  • Hines, M. L., Morse, T., Migliore, M., Carnevale, N. T., & Shepherd, G. M. (2004). ModelDB: a database to support computational neuroscience. Journal of Computational Neuroscience, 17, 7–11.

    Article  PubMed  Google Scholar 

  • Hjorth-Simonsen, A. (1973). Some intrinsic connections of the hippocampus in the rat: an experimental analysis. The Journal of Comparative Neurology, 147, 145–161.

    Article  PubMed  CAS  Google Scholar 

  • Holmes, W. R., Ambros-Ingerson, J., & Grover, L. M. (2006). Fitting experimental data to models that use morphological data from public databases. Journal of Computational Neuroscience, 20, 349–365.

    Article  PubMed  CAS  Google 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.

    CAS  Google Scholar 

  • Ishizuka, N., Cowan, W. M., & Amaral, D. G. (1995). A quantitative analysis of the dendritic organization of pyramidal cells in the rat hippocampus. The Journal of Comparative Neurology, 362, 17–45.

    Article  PubMed  CAS  Google Scholar 

  • Jaffe, D. B., & Carnevale, N. T. (1999). Passive normalization of synaptic integration influenced by dendritic architecture. Journal of Neurophysiology, 82, 3268–3285.

    PubMed  CAS  Google Scholar 

  • Jahr, C. E., & Stevens, C. F. (1990). Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics. The Journal of Neuroscience, 10, 3178–3182.

    PubMed  CAS  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.

    CAS  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.

    CAS  Google Scholar 

  • Káli, S., & Dayan, P. (2000). The involvement of recurrent connections in area CA3 in establishing the properties of place fields: a model. The Journal of Neuroscience, 20, 7463–7477.

    PubMed  Google Scholar 

  • Khazipov, R., Ragozzino, D., & Bregestovski, P. (1995). Kinetics and Mg2+ block of N-methyl-d-aspartate receptor channels during postnatal development of hippocampal CA3 pyramidal neurons. Neuroscience, 69, 1057–1065.

    Article  PubMed  CAS  Google Scholar 

  • Lazarewicz, M. T., Migliore, M., & Ascoli, G. A. (2002). A new bursting model of CA3 pyramidal cell physiology suggests multiple locations for spike initiation. Biosystems, 67, 129–137.

    Article  PubMed  CAS  Google Scholar 

  • Magee, J. C., & Cook, E. P. (2000). Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons. Nature Neuroscience, 3, 895–903.

    Article  PubMed  CAS  Google Scholar 

  • Major, G., Larkman, A. U., Jonas, P., Sakmann, B., & Jack, J. J. B. (1994). Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices. The Journal of Neuroscience, 14, 4613–4638.

    PubMed  CAS  Google Scholar 

  • Marr, D. (1971). Simple memory: a theory for archicortex. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 262, 23–81.

    Article  PubMed  CAS  Google Scholar 

  • Matsuda, S., Kobayashi, Y., & Ishizuka, N. (2004). A quantitative analysis of the laminar distribution of synaptic boutons in field CA3 of the rat hippocampus. Neuroscience Research, 49, 241–252.

    Article  PubMed  Google Scholar 

  • McMahon, D. B., & Barrionuevo, G. (2002). Short- and long-term plasticity of the perforant path synapse in hippocampal area CA3. Journal of Neurophysiology, 88, 528–533.

    PubMed  Google Scholar 

  • Megías, M., Emri, Z., Freund, T. F., & Gulyás, A. I. (2001). Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells. Neuroscience, 102, 527–540.

    Article  PubMed  Google Scholar 

  • Migliore, M., Hoffman, D. A., Magee, J. C., & Johnston, D. (1999). Role of an A-type K+ conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons. Journal of Computational Neuroscience, 7, 5–15.

    Article  PubMed  CAS  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.

    CAS  Google Scholar 

  • Miller, R. G., Jr. (1998). Beyond ANOVA: Basics of applied statistics. New York: Chapman & Hall/CRC.

    Google Scholar 

  • Nicholson, D., Katz, Y., Trana, R., Kath, W. L., Spruston, N., & Geinisman, Y. (2006). Distance-dependent differences in synapse number and AMPA receptor expression in hippocampal CA1 pyramidal neurons. Neuron, 50, 431–442.

    Article  PubMed  CAS  Google Scholar 

  • Palmer, L. M., & Stuart, G. J. (2009). Membrane potential changes in dendritic spines during action potentials and synaptic inputs. The Journal of Neuroscience, 29, 6897–6903.

    Article  PubMed  CAS  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).

  • 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.

  • Rall, W., Burke, R. E., Smith, T. G., Nelson, P. G., & Frank, K. (1967). Dendritic location of synapses and possible mechanisms for the monosynaptic EPSP in motoneurons. Journal of Neurophysiology, 30, 1169–1193.

    PubMed  CAS  Google Scholar 

  • 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.

  • Rolls, E. T. (1996). A theory of hippocampal function in memory. Hippocampus, 6, 601–620.

    Article  PubMed  CAS  Google Scholar 

  • Roth, A., & Häusser, M. (2001). Compartmental models of rat cerebellar Purkinje cells based on simultaneous somatic and dendritic patch-clamp recordings. Journal de Physiologie, 535, 445–472.

    Article  CAS  Google Scholar 

  • Samsonovich, A., & McNaughton, B. L. (1997). Path integration and cognitive mapping in a continuous attractor neural network model. The Journal of Neuroscience, 17, 5900–5920.

    PubMed  CAS  Google Scholar 

  • Scoville, W. B., & Milner, B. (1957). Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery and Psychiatry, 20, 11–21.

    Article  CAS  Google Scholar 

  • Smith, M. A., Ellis-Davies, G. C. R., & Magee, J. C. (2003). Mechanism of the distance-dependent scaling of Schaffer collateral synapses in rat CA1 pyramidal neurons. Journal de Physiologie, 548, 245–258.

    Article  CAS  Google Scholar 

  • Spruston, N., & Johnston, D. (1992). Perforated patch-clamp analysis of the passive membrane properties of three classes of hippocampal neurons. Journal of Neurophysiology, 67, 508–529.

    PubMed  CAS  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.

    CAS  Google Scholar 

  • Svoboda, K., Tank, D. W., & Denk, W. (1996). Direct measurement of coupling between dendritic spines and shafts. Science, 272, 716–719.

    Article  PubMed  CAS  Google Scholar 

  • Swanson, L. W., Wyss, J. M., & Cowan, W. M. (1978). An autoradiographic study of the organization of intrahippocampal association pathways in the rat. The Journal of Comparative Neurology, 181, 681–715.

    Article  PubMed  CAS  Google Scholar 

  • Turner, D. A., Li, X. G., Pyapali, G. K., Ylinen, A., & Buzsáki, G. (1995). Morphometric and electrical properties of reconstructed hippocampal CA3 neurons recorded in vivo. The Journal of Comparative Neurology, 356, 580–594.

    Article  PubMed  CAS  Google Scholar 

  • Vicini, S., Wang, J. F., Li, J. H., Zhu, W. J., Wang, Y. H., Luo, J. H., et al. (1998). Functional and pharmacological differences between recombinant N-methyl-d-aspartate receptors. Journal of Neurophysiology, 79, 555–566.

    PubMed  CAS  Google Scholar 

  • Wallenstein, G. V., & Hasselmo, M. E. (1997). GABAergic modulation of hippocampal population activity: sequence learning, place field development, and the phase precession effect. Journal of Neurophysiology, 78, 393–408.

    PubMed  CAS  Google Scholar 

  • Williams, S. H., & Johnston, D. (1991). Kinetic properties of two anatomically distinct excitatory synapses in hippocampal CA3 pyramidal neurons. Journal of Neurophysiology, 66, 1010–1020.

    PubMed  CAS  Google Scholar 

Download references

Grants

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

Author information

Author notes

  1. Tamara Perez-Rosello & Michele Migliore

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

Authors and 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

Authors
  1. John L. Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tamara Perez-Rosello
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michele Migliore
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Germán Barrionuevo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Giorgio A. Ascoli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giorgio A. Ascoli.

Additional information

Action Editor: Alain Destexhe

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

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10827-010-0304-x

Keywords