Direct measurement of somatic voltage clamp errors in central neurons.
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.
Williams
Stephen R
SR
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK. srw@mrc-lmb.cam.ac.uk
Mitchell
Simon J
SJ
D000818:Animals; D000831:Animals, Newborn; D003712:Dendrites / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology* / Q000528:radiation effects; D008959:Models, Neurological; D019579:Neocortex / Q000166:cytology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012107:Research Design; D013997:Time Factors
D011743:Pyrimidines; C082246:ICI D2788