Neuron
Volume 97, Issue 1, 3 January 2018, Pages 75-82.e3
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Dendritic Spines Prevent Synaptic Voltage Clamp

https://doi.org/10.1016/j.neuron.2017.11.016Get rights and content
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Highlights

  • High spine neck resistance prevents voltage-clamp control of excitatory synapses.

  • Voltage-clamp measurements are severely distorted for spiny neurons.

  • Large single-spine AMPA conductance saturates synaptic current.

Summary

Synapses are the fundamental units of information processing in the mammalian brain. Much of our understanding of their functional properties comes from voltage-clamp analysis, the predominant approach for investigating synaptic physiology. Here, we reveal that voltage clamp is completely ineffective for most excitatory synapses due to spine electrical compartmentalization. Under local dendritic voltage clamp, single-spine activation produced large spine head depolarizations that severely distorted measurements and recruited voltage-dependent channels. To overcome these voltage-clamp errors, we developed an approach to provide new, accurate measurements of synaptic conductance. Single-synapse AMPA conductance was much larger than previously appreciated, producing saturation effects on synaptic currents. We conclude that electrical compartmentalization profoundly shapes both synaptic function and how that function can be assessed with electrophysiological methods.

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