The rate at which signals can be transmitted between single neurons limits the speed of information processing. Cerebellar mossy fibre boutons are able to maintain synchronous neurotransmitter release at very high action potential frequencies, up to ∼ 1 kHz . The neurotransmitter release occurs at the presynaptic active zone and is controlled by highly localised calcium signals. In order to allow reliable, fast synaptic transmission, calcium ions must be cleared from the active zone. However, the exact mechanisms of calcium clearance remain elusive. Despite the recent advances in imaging technology, it is not yet possible to measure localised calcium signals on the nanometre scale. Nevertheless, it is possible to address the impact of localised calcium signals on neurotransmitter release with use of computational modelling. In this study, I established an experimentally constrained model of an active zone of the cerebellar mossy fibre bouton. My simulations revealed that endogenous fixed buffers that have low calcium binding capacity ( ∼ 15 ) and low affinity for binding calcium in combination with mobile buffers with high affinity for binding calcium enable rapid clearance of calcium from the active zone during high-frequency firing. Moreover, during high-frequency firing, slow endogenous mobile buffers prevent build-up of the intracellular calcium concentration. The results presented in this work suggest that reduced calcium buffering speeds active zone calcium signalling, thus allowing high rates of synaptic transmission.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:21290 |
| Date | 23 May 2018 |
| Creators | Jablonski, Lukasz |
| Contributors | Hallermann, Stefan, Köhling, Rüdiger, Schönwiesner, Marc, Leipzig University |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English, German |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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