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<p>Introduction:</p> <p>Calcium (Ca2+) contributes to long-term and short-term synaptic plasticity in many ways and Ca2+ concentrations within the synaptic cleft fluctuate drastically during neuronal activity. Delivery of Ca2+ to the synaptic cleft can be regulated by astrocytes through transporters in their peripheral processes, e.g. through NCX and PMCA. Therefore, astrocytes may affect synaptic plasticity through Ca2+ homeostasis in the synaptic cleft.</p> <p>The main aim of this work is to develop a biophysically realistic computational model of how astrocytes contribute to synaptic plasticity through regulation of synaptic Ca2+ levels. This work builds on recent research [1] which shows that in thin astrocyte processes microdomains of sodium (Na+) and potassium (K+) forms at the perisynaptic cradle during neuronal excitation. The hypothesis that underpins this work is that elevated levels of Na+ at the cradle could potentially reverse the NCX extruder thereby producing a local supply of Ca2+. Efflux of this Ca2+ via the PMCA would dictate Ca2+ homeostasis in the cleft thereby affecting synaptic plasticity. The proposed model will be used to capture this signalling pathway.</p> <p>Preliminary results will be presented which demonstrates that neuronal excitation modulates Ca2+ concentration in the synaptic cleft.</p> <p>Methods:</p> <p>A biophysical model will be developed as a tool to investigate how the efflux of astrocytic Ca2+ effects Ca2+ homeostasis in the synaptic cleft and therefore plasticity. The model will consist of a mathematical framework which is constructed from existing biophysical models, including models for neuronal firing rates, synaptic transmission, astrocyte Ca2+ dynamics, probability of neurotransmitter release and synaptic plasticity.</p> <p>Approach for statistical analysis:</p> <p>In the first instance, model data will be analysed and graphically represented to help visualise how neuronal excitation modulates Ca2+ in the cleft. This approach will continue as more data emerges on the relationship between plasticity, probability of neurotransmitter release, neuronal excitations, postsynaptic potentiation and Ca2+/Na+ levels in the perisynaptic cradle.</p> <p>References: [1] K. Breslin et al., "Potassium and sodium microdomains in thin astroglial processes: A computational model study," PLOS Comput. Biol., vol. 14, no. 5, p. e1006151, May 2018.</p>
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