New methods for quantifying rapidity of action potential onset differentiate neuron types

Abstract

Two new methods for quantifying the rapidity of action potential onset have lower relative standard deviations and better distinguish neuron cell types than current methods. Action potentials (APs) in most central mammalian neurons exhibit sharp onset dynamics. The main views explaining such an abrupt onset differ. Some studies suggest sharp onsets reflect cooperative sodium channels activation, while others suggest they reflect AP backpropagation from the axon initial segment. However, AP onset rapidity is defined subjectively in these studies, often using the slope at an arbitrary value on the phase plot. Thus, we proposed more systematic methods using the membrane potential’s second-time derivative (V¨m) peak width. Here, the AP rapidity was measured for four different cortical and hippocampal neuron types using four quantification methods: the inverse of full-width at the half maximum of the V¨m peak (IFWd2), the inverse of half-width at the half maximum of the V¨m peak (IHWd2), the phase plot slope, and the error ratio method. The IFWd2 and IHWd2 methods show the smallest variation among neurons of the same type. Furthermore, the AP rapidity, using the V¨m peak width methods, significantly differentiates between different types of neurons, indicating that AP rapidity can be used to classify neuron types. The AP rapidity measured using the IFWd2 method was able to differentiate between all four neuron types analyzed. Therefore, the V¨m peak width methods provide another sensitive tool to investigate the mechanisms impacting the AP onset dynamics.

Cortical Neurons Adjust the Action Potential Onset Features as a Function of Stimulus Type

“…The AP parameters were extracted and evaluated from 20 RS and FS somatosensory cortical neurons stimulated via the current clamp, step-and-hold, and frozen noise stimulation paradigms (Figure 2). The rapidity, threshold, amplitude, and width of each neuron type's APs of the first 50 neuronal responses were averaged and contrasted across neuron types and stimulation methods (see Table 1 that the IFWd is a more consistent and reliable method for quantifying AP rapidity than the phase slope method [24]. Thus, AP rapidity refers to the rapidity calculated using the IFWd method throughout this paper.…”

“…Five parameters were calculated for each spike. AP rapidity was calculated using two methods: the inverse full width at half maximum of the 𝑉 peak (IFWd ; [24,25]), and the phase slope method [16]. Notably, a recent previous study conducted by our team showed The frozen noise stimulus is the product of an artificial neural network that mimics post-synaptic current (for more details on frozen noise stimulus see reference [23]).…”

“…V m peak (IFWd 2 ; [24,25]), and the phase slope method [16]. Notably, a recent previous study conducted by our team showed that the IFWd 2 is a more consistent and reliable method for quantifying AP rapidity than the phase slope method [24].…”