Network structure determines patterns of network reorganization during adult neurogenesis

Abstract

New cells are generated throughout life and integrate into the hippocampus via the process of adult neurogenesis. Epileptogenic brain injury induces many structural changes in the hippocampus, including the death of interneurons and altered connectivity patterns. The pathological neurogenic niche is associated with aberrant neurogenesis, though the role of the network-level changes in development of epilepsy is not well understood. In this paper, we use computational simulations to investigate the effect of network environment on structural and functional outcomes of neurogenesis. We find that small-world networks with external stimulus are able to be augmented by activity-seeking neurons in a manner that enhances activity at the stimulated sites without altering the network as a whole. However, when inhibition is decreased or connectivity patterns are changed, new cells are both less responsive to stimulus and the new cells are more likely to drive the network into bursting dynamics. Our results suggest that network-level changes caused by epileptogenic injury can create an environment where neurogenic reorganization can induce or intensify epileptic dynamics and abnormal integration of new cells.Comment: 28 pages, 10 figure