Biophysical basis for three distinct dynamical mechanisms of action potential initiation.
Bottom Line:
Hodgkin identified three classes of neurons with qualitatively different analog-to-digital transduction properties.From this, we conclude that the spike-initiating dynamics associated with each of Hodgkin's classes represent different outcomes in a nonlinear competition between oppositely directed, kinetically mismatched currents.Through detailed analysis of the spike-initiating process, we have explained a fundamental link between biophysical properties and qualitative differences in how neurons encode sensory input.
View Article:
PubMed Central - PubMed
Affiliation: Computational Neurobiology Laboratory, Salk Institute, La Jolla, California, United States of America. prescott@neurobio.pitt.edu
ABSTRACT
Show MeSH
Transduction of graded synaptic input into trains of all-or-none action potentials (spikes) is a crucial step in neural coding. Hodgkin identified three classes of neurons with qualitatively different analog-to-digital transduction properties. Despite widespread use of this classification scheme, a generalizable explanation of its biophysical basis has not been described. We recorded from spinal sensory neurons representing each class and reproduced their transduction properties in a minimal model. With phase plane and bifurcation analysis, each class of excitability was shown to derive from distinct spike initiating dynamics. Excitability could be converted between all three classes by varying single parameters; moreover, several parameters, when varied one at a time, had functionally equivalent effects on excitability. From this, we conclude that the spike-initiating dynamics associated with each of Hodgkin's classes represent different outcomes in a nonlinear competition between oppositely directed, kinetically mismatched currents. Class 1 excitability occurs through a saddle node on invariant circle bifurcation when net current at perithreshold potentials is inward (depolarizing) at steady state. Class 2 excitability occurs through a Hopf bifurcation when, despite net current being outward (hyperpolarizing) at steady state, spike initiation occurs because inward current activates faster than outward current. Class 3 excitability occurs through a quasi-separatrix crossing when fast-activating inward current overpowers slow-activating outward current during a stimulus transient, although slow-activating outward current dominates during constant stimulation. Experiments confirmed that different classes of spinal lamina I neurons express the subthreshold currents predicted by our simulations and, further, that those currents are necessary for the excitability in each cell class. Thus, our results demonstrate that all three classes of excitability arise from a continuum in the direction and magnitude of subthreshold currents. Through detailed analysis of the spike-initiating process, we have explained a fundamental link between biophysical properties and qualitative differences in how neurons encode sensory input. Related in: MedlinePlus |
Related In:
Results -
Collection
getmorefigures.php?uid=PMC2551735&req=5
Mentions: Several lines of experimental evidence support this prediction. First, the response to brief, subthreshold depolarizing pulses was amplified and prolonged relative to the equivalent hyperpolarizing response in class 1 neurons, consistent with effects of a subthreshold inward current (Figure 5A, right); the opposite pattern was observed in class 3 neurons, consistent with effects of a subthrehsold outward current (Figure 5A, left). Second, in voltage clamp, stepping command potential from −70 mV to perithreshold potentials elicited the largest outward current in class 3 neurons, followed by class 2 and class 1 neurons (Figure 5B). The relative positioning of I–V curves plotted from those experiments (Figure 5C) bore a striking resemblance to the relative positioning of I–V curves in the 2D and 3D models (Figure 4); this is especially true if the persistent Na+ current that was blocked by TTX in the aforementioned experiments is taken into account; this current is expressed exclusively in tonic-spiking neurons [26]. Application of 4-AP confirmed the presence of a persistent, low-threshold K+ current in single-spiking lamina I neurons (Figure 5D). |
View Article: PubMed Central - PubMed
Affiliation: Computational Neurobiology Laboratory, Salk Institute, La Jolla, California, United States of America. prescott@neurobio.pitt.edu