Identifying Crucial Parameter Correlations Maintaining Bursting Activity

Recent experimental and computational studies suggest that linearly correlated sets of parameters (intrinsic and synaptic properties of neurons) allow central pattern-generating networks to produce and maintain their rhythmic activity regardless of changing internal and external conditions. To determine the role of correlated conductances in the robust maintenance of functional bursting activity, we used our existing database of half-center oscillator (HCO) model instances of the leech heartbeat CPG. From the database, we identified functional activity groups of burster (isolated neuron) and half-center oscillator model instances and realistic subgroups of each that showed burst characteristics (principally period and spike frequency) similar to the animal. To find linear correlations among the conductance parameters maintaining functional leech bursting activity, we applied Principal Component Analysis (PCA) to each of these four groups. PCA identified a set of three maximal conductances (leak current, Leak; a persistent K current, K2; and of a persistent Na+ current, P) that correlate linearly for the two groups of burster instances but not for the HCO groups. Visualizations of HCO instances in a reduced space suggested that there might be non-linear relationships between these parameters for these instances. Experimental studies have shown that period is a key attribute influenced by modulatory inputs and temperature variations in heart interneurons. Thus, we explored the sensitivity of period to changes in maximal conductances of Leak, K2, and P, and we found that for our realistic bursters the effect of these parameters on period could not be assessed because when varied individually bursting activity was not maintained.Author Summary: Central pattern-generating networks (CPGs) must be remarkably robust, maintaining functional rhythmic activity despite fluctuations in internal and external conditions. Recent experimental evidence suggests that this robustness is achieved by the coordinated regulation of many membrane and synaptic current parameters. Experimental and computational studies showed that linearly correlated sets of such parameters allow CPG neurons to produce and maintain their rhythmic activity. However, the mechanisms that allow multiple parameters to interact, thereby producing and maintaining rhythmic single cell and network activity, are not clear. Here, we use a half-center oscillator (HCO) model that replicates the electrical activity (rhythmic alternating bursting of mutually inhibitory interneurons) of the leech heartbeat CPG to investigate potential relationships between parameters that maintain functional bursting activity in the HCOs and the isolated component neurons (bursters). We found a linearly correlated set of three maximal conductances that maintains functional bursting activity similar to the animal in burster model instances, therefore increasing robustness of bursting activity. In addition, we found that bursting activity was very sensitive to individual variation of these parameters; only correlated changes could maintain the activity type.