Development of GABAergic inputs controls the contribution of maturing neurons to the adult hippocampal network

Abstract

New neurons are continuously generated in the dentate gyrus (DG) in the adult hippocampus, and new granule cells (GCs) have been shown to be necessary for several aspects of learning and memory. Nonetheless, the limited information available regarding the anatomical and physiological development of synaptic inputs onto maturing neurons has restricted our understanding of how new GCs affect cognition. Here, we use photostimulation to demonstrate the time course by which anatomically isolated inhibitory inputs develop onto maturing GCs. We then show that the gradual development of inhibition is sufficient in a computational model to drive learning of novel information in young neurons. Finally, we validate this model observation by using slice physiology to show how inhibition regulates firing probability and plasticity in young GCs. Combined, these data demonstrate that the unique connectivity of immature GCs affords them a functional role that is different from mature neurons in the DG circuit, a distinction that potentially underlies many of the proposed functions of new neurons in the hippocampal network.