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Direct measurement of somatic voltage clamp errors in central neurons

Abstract

The somatic voltage clamp technique has revolutionized understanding of synaptic physiology and the excitability of neurons. Although computer simulations have indicated that the somatic voltage clamp poorly controls voltage in the dendritic tree of neurons, where the majority of synaptic contacts are made, there has not been an experimental description of the performance of the somatic voltage clamp. Here, we directly quantify errors in the measurement of dendritic synaptic input by the somatic voltage clamp using simultaneous whole-cell recordings from the soma and apical dendrite of rat neocortical pyramidal neurons. The somatic voltage clamp did not control voltage at sites other than the soma and distorted measurement of the amplitude, kinetics, slope conductance and reversal potential of synaptic inputs in a dendritic distance–dependent manner. These errors question the use of the somatic voltage clamp as a quantitative tool in dendritic neurons.

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Figure 1: The somatic voltage clamp does not control dendritic simulated EPSCs at near-physiological temperatures (35–37 °C).
Figure 2: Somatic voltage clamp errors at room temperature (24–25 °C).
Figure 3: Somatic recovery of dendritic synaptic charge.
Figure 4: The somatic voltage clamp inaccurately measures the kinetics of dendritic synaptic currents at room temperature.
Figure 5: Dendritic voltage escape influences injected synaptic current.
Figure 6: Distortions of reversal potential and slope conductance.
Figure 7: Failure to separate temporally overlapping excitatory and inhibitory dendritic synaptic conductance.
Figure 8: Errors in the measurement of excitation and inhibition during a barrage of dendritic synaptic activity.

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Acknowledgements

We are grateful to D. Hodgkin for encouragement. This work was supported by the Medical Research Council (UK).

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S.R.W. performed all experiments and data analysis. S.J.M. performed quantal analysis simulations.

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Correspondence to Stephen R Williams.

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Williams, S., Mitchell, S. Direct measurement of somatic voltage clamp errors in central neurons. Nat Neurosci 11, 790–798 (2008). https://doi.org/10.1038/nn.2137

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