BMC Neuroscience© Grein et al; licensee BioMed Central Ltd. 2013 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 10.1186/1471-2202-14-S1-P321

Poster presentation

Long-term potentiation through calcium-mediated N-Cadherin interaction is tightly controlled by the three-dimensional architecture of the synapse

S Grein1 , S Bunse², E Schuman² and G Queisser1  

(1)

Goethe Center for Scientific Computing, Frankfurt am Main, Hessen, Germany

(2)

Max Planck Institute for Brain Research, Frankfurt am Main, Hessen, Germany

G Queisser

Email: gillian.queisser@gcsc.uni-frankfurt.de

Published online: 8 July 2013

The synaptic cleft is an extracellular domain that is capable of relaying a presynaptically received electrical signal by diffusive neurotransmitters to the postsynaptic membrane. The cleft is trans-synaptically bridged by ring-like shaped clusters of pre- and postsynaptically localized calcium-dependent adhesion proteins of the N-Cadherin type and is possibly the smallest intercircuit in nervous systems [1]. The strength of association between the pre- and postsynaptic membranes can account for synaptic plasticity such as long-term potentiation [2]. Through neuronal activity the intra- and extracellular calcium levels are modulated through calcium exchangers embedded in the pre- and postsynaptic membrane. Variations of the concentration of cleft calcium induces changes in the N-Cadherin-zipper, that in synaptic resting states is rigid and tightly connects the pre- and postsynaptic domain. During synaptic activity calcium concentrations are hypothesized to drop below critical thresholds which leads to loosening of the N-Cadherin connections and subsequently "unzips" the Cadherin-mediated connection. These processes may result in changes in synaptic strength [2]. In order to investigate the calcium-mediated N-Cadherin dynamics at the synaptic cleft, we developed a three-dimensional model including the cleft morphology and all prominent calcium exchangers and corresponding density distributions [3–6]. The necessity for a fully three-dimensional model becomes apparent, when investigating the effects of the spatial architecture of the synapse [7], [8]. Our data show, that the localization of calcium channels with respect to the N-Cadherin ring has substantial effects on the time-scales on which the Cadherin-zipper switches between states, ranging from seconds to minutes. This will have significant effects on synaptic signaling. Furthermore we see, that high-frequency action potential firing can only be relayed to the Calcium/N-Cadherin-system at a synapse under precise spatial synaptic reorganization.

References

1.

Sheng M, Hoogenraad CC: The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View. Annu Rev Biochem 2007, 76:823–847.PubMedCrossRef

2.

Tai CY, Kim SA, Schuman EM: Cadherins and synaptic plasticity. Current Opinion in Cell Biology 2008, 20:567–575.PubMedCrossRef

3.

Graham L: Interpretations of data and mechanisms for hippocampal pyramidal cell models. Plenum Publishing Corporation; 1999.

4.

Gabbiani F, Midtgaard J, Knöpfel T: Synaptic Integration in a Model of Cerebellar Granule Cells. Journal of Neurophysiology 1994,72(2):999–1009.PubMed

5.

Jahr CE, Stevens CF: Calcium permeability of the N-methyl-D-aspartate receptor channel in hippocampal neurons in culture. PNAS Neurobiology 1993,90(24):11573–11577.CrossRef

6.

Vaithianathan T, Manivannan K, Kleene R, Bahr BA, Dey MP, Dityatev A, Suppiramaniam V: Single Channel Recordings From Synaptosomal AMPA Receptors. Cell Biochemistry and Biophysics 2005, 42:75–86.PubMedCrossRef

7.

Burette AC, Lesperance T, Crum J, Martone M, Volkmann N, Ellisman MH, Weinberg RJ: Electron Tomographic Analysis of Synaptic Ultrastructure. The Journal of Comparative Neurology 2012, 520:2697–2711.PubMedCrossRef

8.

Chen X, Winters C, Azzam R, Li X, Galbraith JA, Leapman RD, Reese TS: Organization of the core structure of the postsynaptic density. PNAS 2012,105(11):4453–4458.CrossRef