BioMaths Colloquium Series - 2015/16
05 February 2016 - 3pm Maths Seminar Room
(room 224 Talbot Building 2nd floor)
Mathematical modelling of Ca2+ influx and calmodulin activation in dendritic spines: implications for synaptic plasticity
Prof Krasimira Tsaneva-Atanasova
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| from: www.wun.ac.uk |
Our BioMaths Colloquium seminars resume for the winter term, with a great programme! We kick it off with a talk by Prof Krasimira Tsaneva-Atanasova from the College of Engineering, Mathematics and Physical Sciences at the University of Exeter. Krasimira is a Professor of Mathematics for Healthcare and her research is focussed on biomathematics. Her ultimate goals are to develop novel applications of mathematics for improved quantitative healthcare methods.
Abstract
The rise of intracellular calcium concentration [Ca2+] is believed to play a critical role in triggering synaptic plasticity. This is supported by experimental evidence demonstrating that both, synaptic long-term potentiation (LTP) and depression (LTD), are blocked by pharmacological buffering of Ca2+. The importance of intracellular Ca2+ is reflected in the fact that the dynamics of [Ca2+], acting as intermediate signals for induction of plasticity, are a common feature of most biophysical models of STDP.
Calcium-based biophysical models of STDP include a description of the changes in [Ca2+] due to pre- and post-synaptic spiking. Ca2+ sources may depend on the particular synapse to be modelled, but most frequently include: influx via NMDA receptors (NMDARs); influx via Ca2+-permeable AMPA receptors (AMPARs); influx via voltage-gated Ca2+ channels, or Ca2+ release from intracellular stores. Entry of extracellular Ca2+ via postsynaptic membrane ion channels can be dependent on both the postsynaptic membrane-potential and the action of neurotransmitters in the synaptic cleft, therefore biophysical models of STDP often contain descriptions of electrophysiological cell membrane phenomena and AMPAR/NMDAR ligand-gating in response to neuron pair-spiking.
It is an open question how the multiple special and temporal scales involved in intracellular Ca2+ handling within the STDP models affect the plasticity outcomes predicted by these models. Hebbian or associative plasticity is triggered by postsynaptic Ca2+ influx which activates calmodulin and CaMKII. The influx of Ca2+ through voltage-dependent NMDA receptors and Ca2+ channels is regulated by Ca2+ -activated K+ channels (SK-channels) providing negative feedback regulation of postsynaptic [Ca2+]. Using 3-dimensional modelling of Ca2+ and calmodulin dynamics within dendritic spines we show that the non-linear relationship between Ca2+ influx and calmodulin activation endows SK-channels with the ability to “gate” calmodulin activation and therefore the induction of Hebbian synaptic plasticity. Since SK-channels are inhibited by several neuro-modulator receptors including acetylcholine and noradrenaline, the gating of synaptic plasticity by SK-channels could represent a common mechanism by which neuro-modulators control the induction of synaptic plasticity.
The discussions will continue over biscuits and tea/coffee after the seminar.
Calcium-based biophysical models of STDP include a description of the changes in [Ca2+] due to pre- and post-synaptic spiking. Ca2+ sources may depend on the particular synapse to be modelled, but most frequently include: influx via NMDA receptors (NMDARs); influx via Ca2+-permeable AMPA receptors (AMPARs); influx via voltage-gated Ca2+ channels, or Ca2+ release from intracellular stores. Entry of extracellular Ca2+ via postsynaptic membrane ion channels can be dependent on both the postsynaptic membrane-potential and the action of neurotransmitters in the synaptic cleft, therefore biophysical models of STDP often contain descriptions of electrophysiological cell membrane phenomena and AMPAR/NMDAR ligand-gating in response to neuron pair-spiking.
It is an open question how the multiple special and temporal scales involved in intracellular Ca2+ handling within the STDP models affect the plasticity outcomes predicted by these models. Hebbian or associative plasticity is triggered by postsynaptic Ca2+ influx which activates calmodulin and CaMKII. The influx of Ca2+ through voltage-dependent NMDA receptors and Ca2+ channels is regulated by Ca2+ -activated K+ channels (SK-channels) providing negative feedback regulation of postsynaptic [Ca2+]. Using 3-dimensional modelling of Ca2+ and calmodulin dynamics within dendritic spines we show that the non-linear relationship between Ca2+ influx and calmodulin activation endows SK-channels with the ability to “gate” calmodulin activation and therefore the induction of Hebbian synaptic plasticity. Since SK-channels are inhibited by several neuro-modulator receptors including acetylcholine and noradrenaline, the gating of synaptic plasticity by SK-channels could represent a common mechanism by which neuro-modulators control the induction of synaptic plasticity.
The discussions will continue over biscuits and tea/coffee after the seminar.
Hope to see many of you!
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