Voltage- and space-clamp errors associated with the measurement of electrotonically remote synaptic events

Abstract

1. The voltage- and space-clamp errors associated with the use of a somatic electrode to measure current from dendritic synapses are evaluated using both equivalent-cylinder and morphologically realistic models of neuronal dendritic trees. 2. As a first step toward understanding the properties of synaptic current distortion under voltage-clamp conditions, the attenuation of step and sinusoidal voltage changes are evaluated in equivalent cylinder models. Demonstration of the frequency-dependent attenuation of voltage in the cable is then used as a framework for understanding the distortion of synaptic currents generated at sites remote from the somatic recording electrode and measured in the voltage-clamp recording configuration. 3. Increases in specific membrane resistivity (Rm) are shown to reduce steady-state voltage attenuation, while producing only minimal reduction in attenuation of transient voltage changes. Experimental manipulations that increase Rm therefore improve the accuracy of estimates of reversal potential for electrotonically remote synapses, but do not significantly reduce the attenuation of peak current. In addition, increases in Rm have the effect of slowing the kinetics of poorly clamped synaptic currents. 4. The effects of the magnitude of the synaptic conductance and its kinetics on the measured synaptic currents are also examined and discussed. The error in estimating parameters from measured synaptic currents is greatest for synapses with fast kinetics and large conductances. 5. A morphologically realistic model of a CA3 pyramidal neuron is used to demonstrate the generality of the conclusions derived from equivalent cylinder models. The realistic model is also used to fit synaptic currents generated by stimulation of mossy fiber (MF) and commissural/associational (C/A) inputs to CA3 neurons and to estimate the amount of distortion of these measured currents. 6. Anatomic data from the CA3 pyramidal neuron model are used to construct a simplified two-cylinder CA3 model. This model is used to estimate the electrotonic distances of MF synapses (which are located proximal to the soma) and perforant path (PP) synapses (which are located at the distal ends of the apical dendrites) and the distortion of synaptic current parameters measured for these synapses. 7. Results from the equivalent-cylinder models, the morphological CA3 model, and the simplified CA3 model all indicate that the amount of distortion of synaptic currents increases steeply as a function of distance from the soma. MF synapses close to the soma are likely to be subject only to small space-clamp errors, whereas MF synapses farther from the soma are likely to be substantially attenuated.(ABSTRACT TRUNCATED AT 400 WORDS)