Abstract
Neurons spike when their membrane potential exceeds a threshold value. In central neurons, the spike threshold is not constant but depends on the stimulation. Thus, input-output properties of neurons depend both on the effect of presynaptic spikes on the membrane potential and on the dynamics of the spike threshold. Among the possible mechanisms that may modulate the threshold, one strong candidate is Na channel inactivation, because it specifically impacts spike initiation without affecting the membrane potential. We collected voltage-clamp data from the literature and we found, based on a theoretical criterion, that the properties of Na inactivation could indeed cause substantial threshold variability by itself. By analyzing simple neuron models with fast Na inactivation (one channel subtype), we found that the spike threshold is correlated with the mean membrane potential and negatively correlated with the preceding depolarization slope, consistent with experiments. We then analyzed the impact of threshold dynamics on synaptic integration. The difference between the postsynaptic potential (PSP) and the dynamic threshold in response to a presynaptic spike defines an effective PSP. When the neuron is sufficiently depolarized, this effective PSP is briefer than the PSP. This mechanism regulates the temporal window of synaptic integration in an adaptive way. Finally, we discuss the role of other potential mechanisms. Distal spike initiation, channel noise and Na activation dynamics cannot account for the observed negative slope-threshold relationship, while adaptive conductances (e.g. K+) and Na inactivation can. We conclude that Na inactivation is a metabolically efficient mechanism to control the temporal resolution of synaptic integration.
Highlights
Action potentials are initiated when the membrane potential exceeds a threshold value, but this value depends on the stimulation and can be very variable in vivo [1,2,3,4], which has triggered a recent controversy about the origin of this variability [5,6,7]
With threshold adaptation as implied by Na inactivation, effective postsynaptic potential (PSP) are briefer than PSPs and that their shape depends on membrane depolarization
Spikes are generated by sodium channels, which inactivate when the neuron is depolarized, raising the threshold for spike initiation
Summary
Action potentials are initiated when the membrane potential exceeds a threshold value, but this value depends on the stimulation and can be very variable in vivo [1,2,3,4], which has triggered a recent controversy about the origin of this variability [5,6,7]. This phenomenon has been observed in many areas of the nervous system: visual cortex [1,2,3], somatosensory cortex [4]; prefrontal cortex [8]; neostriatum [9], neocortex [10,11], hippocampus [12,13], and auditory brainstem [14,15,16,17]. Our second goal was to evaluate the consequences of threshold dynamics on the integration of postsynaptic potentials (PSPs)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
