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Synaptic amplification by dendritic spines enhances input cooperativity

Abstract

Dendritic spines are the nearly ubiquitous site of excitatory synaptic input onto neurons1,2 and as such are critically positioned to influence diverse aspects of neuronal signalling. Decades of theoretical studies have proposed that spines may function as highly effective and modifiable chemical and electrical compartments that regulate synaptic efficacy, integration and plasticity3,4,5,6,7,8. Experimental studies have confirmed activity-dependent structural dynamics and biochemical compartmentalization by spines9,10,11,12. However, there is a longstanding debate over the influence of spines on the electrical aspects of synaptic transmission and dendritic operation3,4,5,6,7,8,13,14,15,16,17,18. Here we measure the amplitude ratio of spine head to parent dendrite voltage across a range of dendritic compartments and calculate the associated spine neck resistance (Rneck) for spines at apical trunk dendrites in rat hippocampal CA1 pyramidal neurons. We find that Rneck is large enough (500 MΩ) to amplify substantially the spine head depolarization associated with a unitary synaptic input by 1.5- to 45-fold, depending on parent dendritic impedance. A morphologically realistic compartmental model capable of reproducing the observed spatial profile of the amplitude ratio indicates that spines provide a consistently high-impedance input structure throughout the dendritic arborization. Finally, we demonstrate that the amplification produced by spines encourages electrical interaction among coactive inputs through an Rneck-dependent increase in spine head voltage-gated conductance activation. We conclude that the electrical properties of spines promote nonlinear dendritic processing and associated forms of plasticity and storage, thus fundamentally enhancing the computational capabilities of neurons19,20,21.

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Figure 1: Measurement of voltage amplitude ratio across apical trunk spine necks.
Figure 2: Spine neck voltage amplitude ratio varies as a function of dendritic compartment.
Figure 3: Spine-to-branch voltage amplitude ratio is mediated by dendritic impedance.
Figure 4: Spines enhance the cooperative interaction among multiple inputs.

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Acknowledgements

We thank A. Milstein, S. Gale and R. Chitwood for help in creating analysis tools and G. Murphy, S. Williams and D. Johnston for comments on the manuscript. This work was supported by the Howard Hughes Medical Institute, the National Institutes of Health (NS-046064, NS-077601) and the Wellcome Trust (International Senior Research Fellowship to J.K.M., grant number 090915).

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M.T.H., J.K.M. and J.C.M. conceived the project and designed the experiments. M.T.H. and J.K.M. performed all experiments and data analysis. N.S., W.L.K. and J.C.M. performed computer simulations. M.T.H., J.K.M. and J.C.M. wrote the paper with comments from all authors.

Corresponding author

Correspondence to Jeffrey C. Magee.

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The authors declare no competing financial interests.

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Harnett, M., Makara, J., Spruston, N. et al. Synaptic amplification by dendritic spines enhances input cooperativity. Nature 491, 599–602 (2012). https://doi.org/10.1038/nature11554

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