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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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The contribution of calcium conductance and dynamics to distance-dependent correlations.A, Relationship between peak voltage and soma-spine distance in a sample of branches in the CA1 model neuron. B, Relationship between voltage half-width and distance to the soma for same sample of branches shown in A. C, Relationship between voltage integral and distance to the soma for same sample of branches shown in A. D, E, R2 values for combinations of NMDA decay and calcium extrusion time constants for all spines, with and without R-type channels. # indicates an 80% decrease in NMDA decay and in calcium extrusion time constants that are used in all other figures in the manuscript. F, For 80% decrease in values (indicated # in E), relationship between soma-spine distance with peak voltage (left panel), voltage integral (centre panel) and peak calcium in spines (right panel). Correlations for peak voltage and voltage integral remain stable (compared with Fig. 2G, H) but the correlation with peak calcium concentration disappears (comparison with Fig. 2J).
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pcbi-1002545-g005: The contribution of calcium conductance and dynamics to distance-dependent correlations.A, Relationship between peak voltage and soma-spine distance in a sample of branches in the CA1 model neuron. B, Relationship between voltage half-width and distance to the soma for same sample of branches shown in A. C, Relationship between voltage integral and distance to the soma for same sample of branches shown in A. D, E, R2 values for combinations of NMDA decay and calcium extrusion time constants for all spines, with and without R-type channels. # indicates an 80% decrease in NMDA decay and in calcium extrusion time constants that are used in all other figures in the manuscript. F, For 80% decrease in values (indicated # in E), relationship between soma-spine distance with peak voltage (left panel), voltage integral (centre panel) and peak calcium in spines (right panel). Correlations for peak voltage and voltage integral remain stable (compared with Fig. 2G, H) but the correlation with peak calcium concentration disappears (comparison with Fig. 2J).

Mentions: Why is BAP-induced peak calcium consistently the best correlate of soma-synapse distance? Following synapse activation, the initial calcium influx into spines is mediated by AMPA receptors and NMDA receptors that have been partially unblocked by the synaptically-induced depolarisation (Fig. 2B–F). Arrival of the BAP at the spine head causes an additional increase in local membrane potential and calcium influx, via further unblocking of NMDA receptors (Fig. 2B–F). NMDA receptors act as coincidence detectors [41] and require, besides synaptic stimulation, postsynaptic depolarisation, in this case provided by the BAP, to unblock the channel further. This calcium increase due to the BAP is responsible for the distance dependency of peak calcium. Since the calcium influx is dependent on membrane potential (see Eqns. 3–7, Materials and Methods), and the BAP amplitude decreases with distance in the apical shaft (Fig. 2G, Fig. 5A), in agreement with experimental findings [13], [36], there is less BAP-induced calcium influx at distal synapses in the apical shaft than at proximal synapses (Fig. 2C, J). Without a BAP, as in subthreshold stimulation, the NMDA channels remained closed and peak calcium is no longer informative about distance (Fig. 4N).


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)

The contribution of calcium conductance and dynamics to distance-dependent correlations.A, Relationship between peak voltage and soma-spine distance in a sample of branches in the CA1 model neuron. B, Relationship between voltage half-width and distance to the soma for same sample of branches shown in A. C, Relationship between voltage integral and distance to the soma for same sample of branches shown in A. D, E, R2 values for combinations of NMDA decay and calcium extrusion time constants for all spines, with and without R-type channels. # indicates an 80% decrease in NMDA decay and in calcium extrusion time constants that are used in all other figures in the manuscript. F, For 80% decrease in values (indicated # in E), relationship between soma-spine distance with peak voltage (left panel), voltage integral (centre panel) and peak calcium in spines (right panel). Correlations for peak voltage and voltage integral remain stable (compared with Fig. 2G, H) but the correlation with peak calcium concentration disappears (comparison with Fig. 2J).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002545-g005: The contribution of calcium conductance and dynamics to distance-dependent correlations.A, Relationship between peak voltage and soma-spine distance in a sample of branches in the CA1 model neuron. B, Relationship between voltage half-width and distance to the soma for same sample of branches shown in A. C, Relationship between voltage integral and distance to the soma for same sample of branches shown in A. D, E, R2 values for combinations of NMDA decay and calcium extrusion time constants for all spines, with and without R-type channels. # indicates an 80% decrease in NMDA decay and in calcium extrusion time constants that are used in all other figures in the manuscript. F, For 80% decrease in values (indicated # in E), relationship between soma-spine distance with peak voltage (left panel), voltage integral (centre panel) and peak calcium in spines (right panel). Correlations for peak voltage and voltage integral remain stable (compared with Fig. 2G, H) but the correlation with peak calcium concentration disappears (comparison with Fig. 2J).
Mentions: Why is BAP-induced peak calcium consistently the best correlate of soma-synapse distance? Following synapse activation, the initial calcium influx into spines is mediated by AMPA receptors and NMDA receptors that have been partially unblocked by the synaptically-induced depolarisation (Fig. 2B–F). Arrival of the BAP at the spine head causes an additional increase in local membrane potential and calcium influx, via further unblocking of NMDA receptors (Fig. 2B–F). NMDA receptors act as coincidence detectors [41] and require, besides synaptic stimulation, postsynaptic depolarisation, in this case provided by the BAP, to unblock the channel further. This calcium increase due to the BAP is responsible for the distance dependency of peak calcium. Since the calcium influx is dependent on membrane potential (see Eqns. 3–7, Materials and Methods), and the BAP amplitude decreases with distance in the apical shaft (Fig. 2G, Fig. 5A), in agreement with experimental findings [13], [36], there is less BAP-induced calcium influx at distal synapses in the apical shaft than at proximal synapses (Fig. 2C, J). Without a BAP, as in subthreshold stimulation, the NMDA channels remained closed and peak calcium is no longer informative about distance (Fig. 4N).

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