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The interaction between excitation and inhibition is crucial for braincomputation. To understand synaptic mechanisms underlying brain function, it isimportant to separate excitatory and inhibitory inputs to a target neuron. Inthe traditional method, after applying somatic current or voltage clamp, theexcitatory and inhibitory conductances are determined from the synapticcurrent-voltage (I-V) relation --- the slope corresponds to the totalconductance and the intercept corresponds to the reversal current. Because ofthe space clamp effect, the measured conductance in general deviatessubstantially from the local conductance on the dendrite. Therefore, theinterpretation of the conductance measured by the traditional method remains tobe clarified. In this work, based on the investigation of an idealizedball-and-stick neuron model and a biologically realistic pyramidal neuronmodel, we first demonstrate both analytically and numerically that theconductance determined by the traditional method has no clear biologicalinterpretation due to the neglect of a nonlinear interaction between the clampcurrent and the synaptic current across the spatial dendrites. As aconsequence, the traditional method can induce an arbitrarily large error ofconductance measurement, sometimes even leads to unphysically negativeconductance. To circumvent the difficulty of elucidating synaptic impact onneuronal computation using the traditional method, we then propose a frameworkto determine the effective conductance that reflects directly the functionalimpact of synaptic inputs on action potential initiation and thereby neuronalinformation processing. Our framework has been further verified in realisticneuron simulations, thus greatly improves upon the traditional approach byproviding a reliable and accurate assessment of the role of synaptic activityin neuronal computation.

A New Framework for Determination of Excitatory and Inhibitory Conductances Using Somatic Clamp