- Poster presentation
- Open Access
Long-term potentiation through calcium-mediated N-Cadherin interaction is tightly controlled by the three-dimensional architecture of the synapse
BMC Neuroscience volume 14, Article number: P321 (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 . The strength of association between the pre- and postsynaptic membranes can account for synaptic plasticity such as long-term potentiation . 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 . 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 , . 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.
Sheng M, Hoogenraad CC: The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View. Annu Rev Biochem. 2007, 76: 823-847. 10.1146/annurev.biochem.76.060805.160029.
Tai CY, Kim SA, Schuman EM: Cadherins and synaptic plasticity. Current Opinion in Cell Biology. 2008, 20: 567-575. 10.1016/j.ceb.2008.06.003.
Graham L: Interpretations of data and mechanisms for hippocampal pyramidal cell models. 1999, Plenum Publishing Corporation
Gabbiani F, Midtgaard J, Knöpfel T: Synaptic Integration in a Model of Cerebellar Granule Cells. Journal of Neurophysiology. 1994, 72 (2): 999-1009.
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.
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. 10.1385/CBB:42:1:075.
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. 10.1002/cne.23067.
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.
About this article
Cite this article
Grein, S., Bunse, S., Schuman, E. et al. Long-term potentiation through calcium-mediated N-Cadherin interaction is tightly controlled by the three-dimensional architecture of the synapse. BMC Neurosci 14, P321 (2013). https://doi.org/10.1186/1471-2202-14-S1-P321
- Synaptic Cleft
- Postsynaptic Membrane
- Synaptic Strength
- Potential Firing
- Action Potential Firing