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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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Peak spine calcium following backpropagation strongly correlates with EPSP attenuation.A, Relationship between path distance to soma and EPSP attenuation. Coloured circles indicate selected spines (see Fig. 2). B–G, Peak, integral and delay-to-peak voltage and calcium signals as correlates for EPSP attenuation. R2 values indicated for each fit.
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pcbi-1002545-g006: Peak spine calcium following backpropagation strongly correlates with EPSP attenuation.A, Relationship between path distance to soma and EPSP attenuation. Coloured circles indicate selected spines (see Fig. 2). B–G, Peak, integral and delay-to-peak voltage and calcium signals as correlates for EPSP attenuation. R2 values indicated for each fit.

Mentions: From a functional perspective, a more important measure than path distance of a synapse from the soma is the amount of attenuation EPSPs undergo en route to the soma. Although a major factor influencing EPSP attenuation is distance, there are also other factors involved such as dendritic diameter, the activation state of the dendrite and low threshold voltage-gated channels. To test whether attenuation can also be predicted by BAP features, we measured EPSP attenuation for each synapse, defined as the difference in EPSP amplitudes at the synapse and soma, divided by the EPSP amplitude at the soma (see Materials and Methods). As expected it increased with distance from the soma, though the rate of increase with distance reduced in the smaller oblique branches (Fig. 6A). Attenuation depended on the BAP features in the same way as soma-dendritic distance. Again, peak calcium had a strong predictive power (R2 = 0.72, Fig. 6E) while peak voltage and delay-to-peak voltage and calcium were moderately to strongly-correlated (Fig. 6B, D, G). This demonstrates that BAP-induced calcium levels can predict not only soma-synapse distance but also the more physiologically-relevant EPSP attenuation. The integrals of calcium and voltage were also strongly correlated with EPSP attenuation (Fig. 6C, R2 = 0.59, Fig. 6F, R2 = 0.65) due to low variation in attenuation along each oblique dendrite (Fig. 6A).


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)

Peak spine calcium following backpropagation strongly correlates with EPSP attenuation.A, Relationship between path distance to soma and EPSP attenuation. Coloured circles indicate selected spines (see Fig. 2). B–G, Peak, integral and delay-to-peak voltage and calcium signals as correlates for EPSP attenuation. R2 values indicated for each fit.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002545-g006: Peak spine calcium following backpropagation strongly correlates with EPSP attenuation.A, Relationship between path distance to soma and EPSP attenuation. Coloured circles indicate selected spines (see Fig. 2). B–G, Peak, integral and delay-to-peak voltage and calcium signals as correlates for EPSP attenuation. R2 values indicated for each fit.
Mentions: From a functional perspective, a more important measure than path distance of a synapse from the soma is the amount of attenuation EPSPs undergo en route to the soma. Although a major factor influencing EPSP attenuation is distance, there are also other factors involved such as dendritic diameter, the activation state of the dendrite and low threshold voltage-gated channels. To test whether attenuation can also be predicted by BAP features, we measured EPSP attenuation for each synapse, defined as the difference in EPSP amplitudes at the synapse and soma, divided by the EPSP amplitude at the soma (see Materials and Methods). As expected it increased with distance from the soma, though the rate of increase with distance reduced in the smaller oblique branches (Fig. 6A). Attenuation depended on the BAP features in the same way as soma-dendritic distance. Again, peak calcium had a strong predictive power (R2 = 0.72, Fig. 6E) while peak voltage and delay-to-peak voltage and calcium were moderately to strongly-correlated (Fig. 6B, D, G). This demonstrates that BAP-induced calcium levels can predict not only soma-synapse distance but also the more physiologically-relevant EPSP attenuation. The integrals of calcium and voltage were also strongly correlated with EPSP attenuation (Fig. 6C, R2 = 0.59, Fig. 6F, R2 = 0.65) due to low variation in attenuation along each oblique dendrite (Fig. 6A).

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