EXPERIENCE-DEPENDENT REMODELLING OF ADULT-BORN GRANULE CELL CONNECTIVITY IN THE DENTATE GYRUS

Adult hippocampal neurogenesis in the dentate gyrus is shaped by environmental and social inputs, but how these factors influence integration process and connectivity of adult-born granule cells (abGCs) is poorly understood. We previously showed that abGCs of standard-housed (SH) mice exposed for 5 weeks to a classical environmental enrichment paradigm (EE, large hamster cage with objects and running wheels) undergo an expansion of their local and long-range presynaptic connectome during a critical period of plasticity. Using monosynaptic rabies tracing, we now show that this effect is independent from cage geometry or size, but requires a complex enrichment combined with tridimensional (3D) exploratory behaviour. Blocking 3D access prevented the EE-induced connectivity increase, while providing 3D structures in a standard-like cage was sufficient to reproduce the effect. Notably, this connectivity rewiring is distinct form changes in abGC numbers, and is only elicited when the EE is experienced as novelty, as abGCs of mice reared and raised in EE have increased abGC numbers, but fail to rewire their connectome. Chemogenetic manipulation of hippocampal interneurons during EE exposure was sufficient to alter connectivity changes of abGCs, implicating inhibitory networks as key regulatory modulators of abGC circuit plasticity. Extending our analyses to social experience, we found that 5 weeks of social isolation exerted opposite effects to EE, impairing abGC integration and inducing depressive-like behaviour. Together, these findings reveal that both positive and adverse experiences distinctly remodel the presynaptic connectome of abGCs, and thus their role in hippocampal circuit information processing.