Modeling the patch clamp experimental setup to recover undisturbed native electrical signals

Viktor János Oláh1 , Gergely Tarcsay1, János Brunner1

1 Institute of Experimental Medicine, Budapest

Patch clamp recording from small axonal structures became available recently, providing new insights into the mechanisms of neuronal information flow. However, an unresolved difficulty of these electrophysiological measurements is that recorded signals can be highly distorted by any residual capacitance of the recording instruments. In order to explore these signal deteriorations and to retrieve the undisturbed native voltage signal from small axons, we developed a realistic in silico model of the recording instrumentation based on measurements of their electrical components. This complex electrical circuit model simulated the phenomenological behavior of the amplifier and patch pipettes. Combination of this instrumental model together with the reconstructed morphology allowed the estimation of the undisturbed passive membrane properties and the active conductances, which underlie the axonal action potential generation based on voltage recordings from a small hippocampal mossy fiber axon terminal. Furthermore, the simulations recreated the native action potentials after detaching the recording instrumentation from the reconstructed axon that operated with the estimated sodium and potassium conductances. As expected, the results revealed a large reduction in the AP amplitude and deceleration in kinetics due to the filtering effect of patch pipette. However, the model also suggested that the recording instruments interfere with local signal generation. Altogether, our instrumental model can be employed to recover undisturbed electrical signals of the small neuronal structures from the distorted voltage measurements.