Principles for simultaneous measurement of excitatory and inhibitory conductances of single cells in a single trial

Neuronal activity is determined by the interplay between excitatory and inhibitory inputs of individual cells. Whether or not these inputs covary over time or between repeated stimuli remains unclear due to the lack of experimental methods for measuring both inputs at the same time. Current methods for conductance measurement are based on repeatedly stimulating neurons while holding their membrane potential at different levels so to reveal either excitation or inhibition, which can only provide the averaged relationship between the two. Here we develop a new framework for simultaneously measuring both the excitatory and inhibitory inputs of single cells in a single trial under current clamp. This method is based on theoretical analysis of passive circuits and can be practically achieved by injecting a high frequency sinusoidal current and then analysing the data using an optimization algorithm. We use simulations to demonstrate the ability of this approach to reveal the excitatory and inhibitory inputs of point neurons, in which we mimic adapting sensory inputs as well as an asynchronous balanced state.