Functional convergence of developmentally and adult‐generated granule cells in dentate gyrus circuits supporting hippocampus‐dependent memory

Abstract

In the hippocampus, the production of dentate granule cells (DGCs) persists into adulthood. As adult‐generated neurons are thought to contribute to hippocampal memory processing, promoting adult neurogenesis therefore offers the potential for restoring mnemonic function in the aged or diseased brain. Within this regenerative context, one key issue is whether developmentally generated and adult‐generated DGCs represent functionally equivalent or distinct neuronal populations. To address this, we labeled separate cohorts of developmentally generated and adult‐generated DGCs and used immunohistochemical approaches to compare their integration into circuits supporting hippocampus‐dependent memory in intact mice. First, in the water maze task, rates of integration of adult‐generated DGCs were regulated by maturation, with maximal integration not occurring until DGCs were five or more weeks in age. Second, these rates of integration were equivalent for embryonically, postnatally, and adult‐generated DGCs. Third, these findings generalized to another hippocampus‐dependent task, contextual fear conditioning. Together, these experiments indicate that developmentally generated and adult‐generated DGCs are integrated into hippocampal memory networks at similar rates, and suggest a functional equivalence between DGCs generated at different developmental stages.