Morphogenic impact of excitatory-inhibitory interaction on the structure of neuronal networks

• Applicant: Dr. Samora Okujeni
• Subject Area: Experimental and Theoretical Network Neuroscience ; Developmental Neurobiology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 516753473

The self-organization of neuronal networks is based on activity-dependent structural and functional differentiation processes such as cell migration, neurite outgrowth and the maturation of inhibition. Using computational models of neurite growth and migration in neuronal networks and networks of cortical neurons developing in vitro, we will study how inhibition contributes to the differentiation of the mesoscale architecture of neuronal networks. We recently proposed that neurons may either grow or migrate to establish the neurite field overlap necessary to attain a hypothetical target level of connectivity and activity. Herein, excitatory neurons attract each other, leading to varying degrees of clustering in silico and in vitro dependent on the relationship between migration and neurite outgrowth rates. In this project we will extend this framework and investigate how the maturation of inhibition during early postnatal development modulates the homeostatically regulated structural differentiation of neuronal networks. Preliminary findings of simulated network development indicate that inhibitory synaptic input would act repellent for other neurons within the migratory process but would promote neurite outgrowth, which predicts a series of interesting effects on developing network architectures: (i) Inhibition would promote connectivity beyond the level necessary for activity homeostasis in merely excitatory networks. (ii) The fraction of inhibitory neurons in a local population of neurons would have crucial impact on their embedding into the larger network. Inhibition would thereby promote larger interaction horizons, formation of network hubs and small-world connectivity at the network level. (iii) Asymmetric interactions between excitatory and inhibitory neurons would lead to clusters of excitatory neurons being surrounded by inhibitory neurons as described for the micro-columnar organization of the neocortex. Inhibition thereby would contribute to the structural and functional modularization of neuronal networks. The project will provide new perspectives on the complex interaction between migration, neurite outgrowth and inhibition in the regulation of neuronal network architecture and activity. Disentangling such interaction would be highly relevant to understand the native self-organization of neuronal tissue and its reorganization in neurodegenerative processes.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Ulrich Egert