Adult neurogenesis and synaptic rewiring in the hippocampal dentate gyrus

Van Ooyen, A., Teuchert-Noodt, G., Grafen, K., and Butz-Ostendorf, 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. 389-408.

Abstract

New neurons are continuously generated in the dentate gyrus (DG) of the hippocampus throughout life. This adult neurogenesis is accompanied by synaptogenesis as newborn cells become integrated into the hippocampal circuitry. An important question is to what extent young neurons thereby rewire the synaptic connectivity of preexisting networks.

Here we describe a combined experimental and computational study that we carried out to address this question. Synaptic rewiring, as characterized by autophagic degradation of remodeling axon terminals, was measured in the DG of gerbils that had different rates of cell proliferation (CP) as a result of different rearing conditions or pharmacological treatment. Surprisingly, we found that higher proliferation rates led to less synaptic rewiring. To help explain this finding, we used a novel computational model of the DG that incorporates neurogenesis, apoptosis, and activity-dependent synaptogenesis. In the model, each neuron regulates its synapse formation and deletion so as to try and reach a set point level of electrical activity (homeostasis). This need for activity homeostasis was shown to give rise to diminished synaptic rewiring when CP rates were high.

In general, homeostatic regulation of activity may be a pivotal organizing principle of neuronal networks, governing not only the formation of synaptic connectivity during development but also its reorganization during adulthood.