Neurodegeneration progressively removes synapses and neurons, yet neural circuits can retain stable collective dynamics despite substantial structural loss. Which structural principles confer this resilience remained unclear. Using large-scale spiking networks spanning empirical and synthetic microcircuit architectures, we systematically compared synaptic and neuronal modes of degeneration under controlled pruning strategies. We found that resilience was not determined by connectivity loss alone, but by how inhibitory gain was embedded within circuit architecture. Networks in which inhibitory neurons occupied structurally central positions robustly maintained health-like firing rates, levels of synchrony, and informational bandwidth across degeneration stages, whereas architectures lacking such embedding exhibited amplified dynamical disruption. Across regimes, the evolution of activity was organized by a compact set of weight-aware structural descriptors that generalized across network sizes and classes, with total effective synaptic coupling providing a dominant organizing axis. These results identified inhibitory architecture as a mechanistic determinant of circuit resilience and provided a predictive framework linking structural degeneration to collective dynamics.
Mengiste, S. A. A., Aertsen, A., Kumar, A., Battaglia, D. A.
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