Limits...
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.

Show MeSH

Related in: MedlinePlus

The effect of asynchronous inputs and subthreshold inputs on features tested.Colours indicate spine locations shown in Fig. 2. A–H, Asynchronous inputs (240 synapses): In each of 100 simulations, the cell was presented with synaptic inputs whose activation times were randomly drawn from a 10 ms window. A, E, Example voltage and calcium traces of spines indicated in Fig. 2A. B–D, F–H, Peak, integral, and delay-to-peak voltage and calcium changes at all asynchronously-activated spines across the dendritic tree plotted against path distance. I–P, Subthreshold inputs (170 synapses): I, M, Synaptically-stimulated changes in voltage and calcium at selected spines (see Fig. 2); J–L, N–P, Peak, integral and delay-to-peak voltage and calcium changes in spines following subthreshold stimulation plotted against path distance.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3375220&req=5

pcbi-1002545-g004: The effect of asynchronous inputs and subthreshold inputs on features tested.Colours indicate spine locations shown in Fig. 2. A–H, Asynchronous inputs (240 synapses): In each of 100 simulations, the cell was presented with synaptic inputs whose activation times were randomly drawn from a 10 ms window. A, E, Example voltage and calcium traces of spines indicated in Fig. 2A. B–D, F–H, Peak, integral, and delay-to-peak voltage and calcium changes at all asynchronously-activated spines across the dendritic tree plotted against path distance. I–P, Subthreshold inputs (170 synapses): I, M, Synaptically-stimulated changes in voltage and calcium at selected spines (see Fig. 2); J–L, N–P, Peak, integral and delay-to-peak voltage and calcium changes in spines following subthreshold stimulation plotted against path distance.

Mentions: As with synchronous synaptic stimulation, peak voltage in asynchronously-activated spines was weakly correlated with distance (R2 = 0.23, Fig. 4B). Both delay-to-peak voltage and delay-to-peak calcium also showed moderate or weak correlation with distance (Fig. 4D, R2 = 0.53, Fig. 4H, R2 = 0.32). Integral voltage and integral calcium continued to contain a moderate amount of distance information (Fig. 4C, R2 = 0.50, Fig. 4G, R2 = 0.60). However, these correlations were still lower than peak calcium, which remained the strongest correlate with dendritic distance (Fig. 4F, R2 = 0.65).


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 effect of asynchronous inputs and subthreshold inputs on features tested.Colours indicate spine locations shown in Fig. 2. A–H, Asynchronous inputs (240 synapses): In each of 100 simulations, the cell was presented with synaptic inputs whose activation times were randomly drawn from a 10 ms window. A, E, Example voltage and calcium traces of spines indicated in Fig. 2A. B–D, F–H, Peak, integral, and delay-to-peak voltage and calcium changes at all asynchronously-activated spines across the dendritic tree plotted against path distance. I–P, Subthreshold inputs (170 synapses): I, M, Synaptically-stimulated changes in voltage and calcium at selected spines (see Fig. 2); J–L, N–P, Peak, integral and delay-to-peak voltage and calcium changes in spines following subthreshold stimulation plotted against path distance.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002545-g004: The effect of asynchronous inputs and subthreshold inputs on features tested.Colours indicate spine locations shown in Fig. 2. A–H, Asynchronous inputs (240 synapses): In each of 100 simulations, the cell was presented with synaptic inputs whose activation times were randomly drawn from a 10 ms window. A, E, Example voltage and calcium traces of spines indicated in Fig. 2A. B–D, F–H, Peak, integral, and delay-to-peak voltage and calcium changes at all asynchronously-activated spines across the dendritic tree plotted against path distance. I–P, Subthreshold inputs (170 synapses): I, M, Synaptically-stimulated changes in voltage and calcium at selected spines (see Fig. 2); J–L, N–P, Peak, integral and delay-to-peak voltage and calcium changes in spines following subthreshold stimulation plotted against path distance.
Mentions: As with synchronous synaptic stimulation, peak voltage in asynchronously-activated spines was weakly correlated with distance (R2 = 0.23, Fig. 4B). Both delay-to-peak voltage and delay-to-peak calcium also showed moderate or weak correlation with distance (Fig. 4D, R2 = 0.53, Fig. 4H, R2 = 0.32). Integral voltage and integral calcium continued to contain a moderate amount of distance information (Fig. 4C, R2 = 0.50, Fig. 4G, R2 = 0.60). However, these correlations were still lower than peak calcium, which remained the strongest correlate with dendritic distance (Fig. 4F, R2 = 0.65).

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