RT Journal Article SR Electronic T1 Microcircuit Synchronization and Heavy-Tailed Synaptic Weight Distribution Augment preBötzinger Complex Bursting Dynamics JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 240 OP 260 DO 10.1523/JNEUROSCI.1195-22.2022 VO 43 IS 2 A1 Ashhad, Sufyan A1 Slepukhin, Valentin M. A1 Feldman, Jack L. A1 Levine, Alex J. YR 2023 UL http://www.jneurosci.org/content/43/2/240.abstract AB The preBötzinger Complex (preBötC) encodes inspiratory time as rhythmic bursts of activity underlying each breath. Spike synchronization throughout a sparsely connected preBötC microcircuit initiates bursts that ultimately drive the inspiratory motor patterns. Using minimal microcircuit models to explore burst initiation dynamics, we examined the variability in probability and latency to burst following exogenous stimulation of a small subset of neurons, mimicking experiments. Among various physiologically plausible graphs of 1000 excitatory neurons constructed using experimentally determined synaptic and connectivity parameters, directed Erdős-Rényi graphs with a broad (lognormal) distribution of synaptic weights best captured the experimentally observed dynamics. preBötC synchronization leading to bursts was regulated by the efferent connectivity of spiking neurons that are optimally tuned to amplify modest preinspiratory activity through input convergence. Using graph-theoretic and machine learning-based analyses, we found that input convergence of efferent connectivity at the next-nearest neighbor order was a strong predictor of incipient synchronization. Our analyses revealed a crucial role of synaptic heterogeneity in imparting exceptionally robust yet flexible preBötC attractor dynamics. Given the pervasiveness of lognormally distributed synaptic strengths throughout the nervous system, we postulate that these mechanisms represent a ubiquitous template for temporal processing and decision-making computational motifs.SIGNIFICANCE STATEMENT Mammalian breathing is robust, virtually continuous throughout life, yet is inherently labile: to adapt to rapid metabolic shifts (e.g., fleeing a predator or chasing prey); for airway reflexes; and to enable nonventilatory behaviors (e.g., vocalization, breathholding, laughing). Canonical theoretical frameworks—based on pacemakers and intrinsic bursting—cannot account for the observed robustness and flexibility of the preBötzinger Complex rhythm. Experiments reveal that network synchronization is the key to initiate inspiratory bursts in each breathing cycle. We investigated preBötC synchronization dynamics using network models constructed with experimentally determined neuronal and synaptic parameters. We discovered that a fat-tailed (non-Gaussian) synaptic weight distribution—a manifestation of synaptic heterogeneity—augments neuronal synchronization and attractor dynamics in this vital rhythmogenic network, contributing to its extraordinary reliability and responsiveness.