Adult-born neurons inhibit developmentally-born neurons during spatial learning

Ongoing neurogenesis in the dentate gyrus (DG) subregion of the hippocampus results in a heterogenous population of neurons. Immature adult-born neurons (ABNs) have physiological and anatomical properties that may give them a unique role in learning. For example, compared to older granule neurons, they have greater somatic excitability, which could facilitate their recruitment into memory traces. However, recruitment is also likely to depend on interactions with other DG neurons through processes such as lateral inhibition. Immature ABNs target inhibitory interneurons and, compared to older neurons, they receive less GABAergic inhibition. Thus, they may induce lateral inhibition of mature DG neurons while being less susceptible to inhibition themselves. To test this we used a chemogenetic approach to silence immature ABNs as rats learned a spatial water maze task, and measured activity (Fos expression) in ABNs and developmentally-born neurons (DBNs). A retrovirus expressing the inhibitory DREADD receptor, hM4Di, was injected into the dorsal DG of male rats at 6w to infect neurons born in adulthood. Animals were also injected with BrdU to label DBNs or ABNs. DBNs were significantly more active than immature 4-week-old ABNs. Silencing 4-week-old ABNs did not alter learning but it increased activity in DBNs. However, silencing ABNs did not affect activation in other ABNs within the DG. Silencing ABNs also did not alter Fos expression in parvalbumin- and somatostatin-expressing interneurons. Collectively, these results suggest that ABNs may directly inhibit DBN activity during hippocampal-dependent learning, which may be relevant for maintaining sparse hippocampal representations of experienced events.