A non-linear regression analysis method for quantitative resolution of the stimulus-evoked compound action potential...

The stimulus-evoked compound action potential (CAP) recorded from rodent optic nerve is polyphasic in profile, with total area under the CAP an index of nerve function. A decrease in CAP area signifies a decrease in the number of axons contributing to the CAP. A disadvantage of considering the CAP a uniform entity is that any distinctions between the axon-subpopulations contributing to the individual peaks go undetected. We illustrate two instances that demonstrate the advantages of resolving the CAP into its constituent peaks. The individual peaks of the CAP were quantified using curve-fitting procedures to describe the CAP as the sum of multiple Gaussian functions. The first example illustrates that the individual peaks comprising the CAP exhibit differential sensitivities to glucopenia, suggesting that the axons within the nerve cannot be considered a homogeneous population with regard to their metabolic characteristics. The second example illustrates that the complex waveform of the CAP recorded from the optic nerve of the hypomyelinated rumpshaker mutant mouse, comprising both positive and negative overlapping peaks, can be resolved into five individual peaks. In conclusion we show that assessing each individual peak of the CAP is a powerful analytic tool for identifying heterogeneous profiles of axon-subpopulations in the rodent optic nerve.