Modifications in network structure and excitability may drive differential activity dependent integration of granule cells into dentate gyrus circuits during normal and pathological adult neurogenesis

Skilling, Q., Roach, J., Althaus, A. L., Murphy, G. G., Sander, L., and Zochowski, M. (2017). In: Van Ooyen, A., and Butz-Ostendorf, M., eds. The Rewiring Brain: A Computational Approach to Structural Plasticity in the Adult Brain. San Diego: Academic Press, pp. 409-423.

Abstract

The granule cells born during adult neurogenesis in the Dentate Gyrus (DG) are thought to be involved in formation of new memory representations. At the same time, they are implicated in exacerbation of the pathology during epilepsy. Moreover, it has been found that patterns of their integration into DG circuits are significantly different in health and pathology. The aim of this contribution is to identify network-wide structural and dynamical mechanisms underlying this differential incorporation of the newly born cells, as well as resulting changes in activity patterns in the network.

We show that, on the one hand, decreased network-wide inhibition and long-range excitatory connectivity alone can result in significant changes in augmentation patterns of new cells, such as increased survival rate of new cells, emergence of globally synchronized activity patterns, and decreased correlation between network drive and location of the surviving cells. On the other hand, we show that changes in excitability, namely phase response curves, of newly born cells can also lead to emergence of globally coherent activity patterns that are not responsive to local input properties. These results indicate that both of these mechanisms can be responsible for reorganization of neuronal pathological integration during adult neurogenesis.