Circuit remodeling by adult neurogenesis: Activity-dependent synaptic competition

Cohorts of adult-born granule cells (aGCs) integrate continuously into the adult hippocampal circuits, generating new connections onto their target cells, which include CA3 pyramidal cells and interneurons. Recent studies from our lab have shown that activation of young (4-week-old) aGCs induces persistent place cell remapping and increased pyramidal cell recruitment in the CA3 region. Together with previous electron microscopy studies, these results suggest that aGCs establish their target connections onto pyramidal cells through activity-dependent competition against preexisting synapses. To test this hypothesis, we studied the structural characteristics of neighboring axonal mossy fiber boutons (MFBs) from young and mature aGCs (“young MFBs” and “mature MFBs”) under conditions of persistent activation of the young cohort. Chronic in vivo optogenetic stimulation of young aGCs induced a substantial reduction in the size of neighboring mature MFBs. However, MFB size was unchanged in boutons farther from active terminals. Electrophysiological recordings to test whether these structural changes are accompanied by the corresponding functional changes in synaptic strength are currently ongoing. These findings support a role for activity-dependent competition in the integration of aGCs, highlighting adult hippocampal neurogenesis as a mechanism that perturbs CA3 network homeostasis by providing a continuous drive for remodeling that favors dynamic encoding.