Method of experimental synaptic conductance estimation: Limitations of the basic approach and extension to voltage-dependent conductances

Abstract

Abstract Estimating the synaptic conductances impinging on a single neuron is one of the open problems that need to be solved in order to understand the flow of information in the brain. Conventional method of evaluating excitatory and inhibitory synaptic conductances has some limitations due to incorrect assumptions about the voltage independence of the conductances. The limitations of the basic method and its generalization to NMDA receptors are the focus of this study. Using numerical simulations with a passive neuron, the effects of different aspects on the residual error—voltage-clamp versus current-clamp modes, linearity of the current–voltage relationship, NMDA receptor contribution, and noise contamination—are investigated. In addition, the effectiveness of experimental tests using the voltage reconstruction method is challenged. In the range of physiologically plausible parameters, the basic method reveals qualitatively wrong modulation of the excitatory and inhibitory conductances. A modified method of estimating voltage-independent AMPA- and GABA-receptor-mediated conductances and voltage-dependent NMDA-receptor-mediated conductances is proposed. This method requires voltage-clamp recordings at three voltage levels, and its estimations of oscillating conductances are accurate. Therefore, the modified method can be recommended for experiments, particularly those involving evaluation of excitatory and inhibitory synaptic conductance modulation in the visual cortex. The basic method, however, compromises the results of excitation and inhibition counterphase modulation during grating visual stimulation of a cat’s striate cortex because it does not account for the NMDA component.