Computational modeling predicts regulation of central pattern generator oscillations by size and density of the...

Central pattern generators are characterized by a heterogeneous cellular composition, with different cell types playing distinct roles in the production and transmission of rhythmic signals. However, little is known about the functional implications of individual variation in the relative distributions of cells and their connectivity patterns. Here, we addressed this question through a combination of morphological data analysis and computational modeling, using the pacemaker nucleus of the weakly electric fish Apteronotus leptorhynchus as case study. A neural network comprised of 60-110 interconnected pacemaker cells and 15-30 relay cells conveying its output to electromotoneurons in the spinal cord, this nucleus continuously generates neural signals at frequencies of up to 1 kHz with high temporal precision. We systematically explored the impact of network size and density on oscillation frequencies and their variation within and across cells. To accurately determine effect sizes, we minimized the likelihood of complex dynamics using a simplified setup precluding differential delays. To identify natural constraints, parameter ranges were extended beyond experimentally recorded numbers of cells and connections. Simulations revealed that pacemaker cells have higher frequencies and lower within-population variability than relay cells. Within-cell precision and between-cells frequency synchronization increased with the number of pacemaker cells and of connections of either type, and decreased with relay cell count in both populations. Network-level frequency-synchronized oscillations occurred in roughly half of simulations, with maximized likelihood and firing precision within biologically observed parameter ranges. These findings suggest the structure of the biological pacemaker nucleus is optimized for generating synchronized sustained oscillations.