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Spine calcium transients induced by synaptically-evoked action potentials can predict synapse location and establish synaptic democracy.

Sterratt DC, Groen MR, Meredith RM, van Ooyen A - PLoS Comput. Biol. (2012)

Bottom Line: Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree.Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value.We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy.

View Article: PubMed Central - PubMed

Affiliation: Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.

ABSTRACT
CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called "synaptic democracy". How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy.

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Synaptic democracy established using homeostatic rules based on peak calcium levels.A, Schematic showing the homeostatic regulation of synaptic strength, defined as AMPA conductance, by peak calcium. B, Peak calcium in spines during the time-lapse homeostatic simulation. Synapses are colour-coded and grouped according to distance. The black dotted line indicates the target level. C, Synaptic strength stabilises during a simulation run of 500 trials. As in B, synapses are grouped and colour-coded according to distance. D, Synaptic strength at the beginning (black crosses) and at the end of the scaling simulation (closed circles) plotted against distance. Black circles indicate the apical shaft, grey circles the oblique dendrites. E, EPSP amplitude at the soma of individual synapses plotted against distance at the start of the simulation. F, EPSP amplitude at the soma of individual synapses plotted against distance at the end of the simulation.
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pcbi-1002545-g008: Synaptic democracy established using homeostatic rules based on peak calcium levels.A, Schematic showing the homeostatic regulation of synaptic strength, defined as AMPA conductance, by peak calcium. B, Peak calcium in spines during the time-lapse homeostatic simulation. Synapses are colour-coded and grouped according to distance. The black dotted line indicates the target level. C, Synaptic strength stabilises during a simulation run of 500 trials. As in B, synapses are grouped and colour-coded according to distance. D, Synaptic strength at the beginning (black crosses) and at the end of the scaling simulation (closed circles) plotted against distance. Black circles indicate the apical shaft, grey circles the oblique dendrites. E, EPSP amplitude at the soma of individual synapses plotted against distance at the start of the simulation. F, EPSP amplitude at the soma of individual synapses plotted against distance at the end of the simulation.

Mentions: We investigated whether homeostatic scaling governed by peak calcium levels could produce a synaptic democracy. Based on the results of the scaled synapse simulations described above (Fig. 7D), we set the target peak calcium value (see Eqn. 9) for all spines at 47.0 µM. Initially, all synapses had the same strength (i.e., AMPA conductance). After each simulation run, the synaptic strength of each synapse was increased or decreased depending on whether the peak calcium value in the spine was lower or higher, respectively, than the target peak calcium level (Fig. 8A, Eqn. 9). Note that in this simulation, synapses were updated once they were activated regardless of whether the response was sub- or suprathreshold (Fig. S4). After 500 runs, the synaptic strengths had reached a stable arrangement in which the distal synapses had higher synaptic strengths than the proximal ones (Fig. 8 C, D, Fig. S4).


Spine calcium transients induced by synaptically-evoked action potentials can predict synapse location and establish synaptic democracy.

Sterratt DC, Groen MR, Meredith RM, van Ooyen A - PLoS Comput. Biol. (2012)

Synaptic democracy established using homeostatic rules based on peak calcium levels.A, Schematic showing the homeostatic regulation of synaptic strength, defined as AMPA conductance, by peak calcium. B, Peak calcium in spines during the time-lapse homeostatic simulation. Synapses are colour-coded and grouped according to distance. The black dotted line indicates the target level. C, Synaptic strength stabilises during a simulation run of 500 trials. As in B, synapses are grouped and colour-coded according to distance. D, Synaptic strength at the beginning (black crosses) and at the end of the scaling simulation (closed circles) plotted against distance. Black circles indicate the apical shaft, grey circles the oblique dendrites. E, EPSP amplitude at the soma of individual synapses plotted against distance at the start of the simulation. F, EPSP amplitude at the soma of individual synapses plotted against distance at the end of the simulation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375220&req=5

pcbi-1002545-g008: Synaptic democracy established using homeostatic rules based on peak calcium levels.A, Schematic showing the homeostatic regulation of synaptic strength, defined as AMPA conductance, by peak calcium. B, Peak calcium in spines during the time-lapse homeostatic simulation. Synapses are colour-coded and grouped according to distance. The black dotted line indicates the target level. C, Synaptic strength stabilises during a simulation run of 500 trials. As in B, synapses are grouped and colour-coded according to distance. D, Synaptic strength at the beginning (black crosses) and at the end of the scaling simulation (closed circles) plotted against distance. Black circles indicate the apical shaft, grey circles the oblique dendrites. E, EPSP amplitude at the soma of individual synapses plotted against distance at the start of the simulation. F, EPSP amplitude at the soma of individual synapses plotted against distance at the end of the simulation.
Mentions: We investigated whether homeostatic scaling governed by peak calcium levels could produce a synaptic democracy. Based on the results of the scaled synapse simulations described above (Fig. 7D), we set the target peak calcium value (see Eqn. 9) for all spines at 47.0 µM. Initially, all synapses had the same strength (i.e., AMPA conductance). After each simulation run, the synaptic strength of each synapse was increased or decreased depending on whether the peak calcium value in the spine was lower or higher, respectively, than the target peak calcium level (Fig. 8A, Eqn. 9). Note that in this simulation, synapses were updated once they were activated regardless of whether the response was sub- or suprathreshold (Fig. S4). After 500 runs, the synaptic strengths had reached a stable arrangement in which the distal synapses had higher synaptic strengths than the proximal ones (Fig. 8 C, D, Fig. S4).

Bottom Line: Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree.Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value.We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy.

View Article: PubMed Central - PubMed

Affiliation: Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, Edinburgh, Scotland, United Kingdom.

ABSTRACT
CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called "synaptic democracy". How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy.

Show MeSH
Related in: MedlinePlus