# Cortical Neurons Adjust the Action Potential Onset Features as a Function of Stimulus Type  
[PERSON]  
1 Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University,  
Riyadh 12372, Saudi Arabia; [EMAIL_ADDRESS]  
1 Correspondence: [EMAIL_ADDRESS]  
2  
[PERSON]  
1 Department of Biomedical Technology, College of Applied Medical Sciences, King Saud University,  
Riyadh 12372, Saudi Arabia; [EMAIL_ADDRESS]  
1
Footnote 1: email: {[PERSON], [PERSON], [PERSON], [PERSON]  
communication channel between two neurons, temporal coding is more effective than spike coding regarding the data rate that can be achieved at a specific frequency [9; 10]. Previous studies have shown that different neuron types can detect subtle stimulus changes by adjusting their firing timing. For instance, neuronal oscillations improve the action potential (AP) precision in mammalian neurons, regardless of neuron type [11], while background noise improves tone discrimination in Parvalbumin-positive neurons in the primary auditory cortex [12]. Conversely, blocking inhibition in a random cortical network reduces the variability evoked by repeated stimulus [13]. Alternatively, several studies have shown that altering the AP shape can manifest neuronal encoding. For instance, stimulus history was shown as more reliably encoded in the AP shape rather than the neuron firing rate [13], and input synchrony was facilitated by changes in the axonal AP amplitude [13]. Regardless of whether variability is observed in the AP shape or firing rate, neuronal response variability can benefit information processing and indicate neurological and psychiatric disorders such as autism [8; 14].  
Mammalian neurons, particularly in the cortex, have distinct AP onset characteristics: rapid AP onset and threshold variability. Several mechanisms have been suggested to account for the two unique features, such as AP backpropagation [15], voltage-gated sodium channels (Nav) cooperative gating [16], and neuron geometry [17]. AP backpropagation, from the AP initiation site at the axon initial segment (AIS) to the soma, increases threshold variability, possibly indicating the distance difference between the initiation site and the soma [15; 18]. Other studies have linked threshold variability to the inactivation of Nav due to prior spikes [19]. However, the precise mechanisms underlying the threshold variability and rapid AP onset, and their implications for the overall network function, remain actively investigated.  
This study investigates how different stimulus types affect the AP shape, particularly AP onset parameters, in two types of cortical neurons. Here, we attempt to answer two questions: (1) do neurons change their AP shape in response to different stimuli (step-and-hold current vs. frozen noise current), and (2) do both neuron types (RS and FS) display similar AP shape changes due to different stimuli? Our results show that AP properties change significantly with each stimulus type. However, some changes are only observed in RS pyramidal neurons, not FS neurons. AP rapidity and threshold variability, in particular, are significantly higher when pyramidal neurons are evoked by noisy input compared to the constant step current, while FS neurons elicit similar AP rapidity regardless of the stimulus type. These differences in AP initiation parameters in response to different stimuli may indicate that different mechanisms govern how cortical neurons encode different stimuli.