Impaired dendritic development and synaptic formation of postnatal-born dentate gyrus granular neurons in the absence of brain-derived neurotrophic factor signaling

Abstract

Neurons are continuously added to the hippocampal dentate gyrus throughout life. These neurons must develop dendritic arbors and spines by which they form synapses for making functional connections with existing neurons. The molecular mechanisms that regulate dendritic development and synaptic formation of postnatal-born granular neurons in the dentate gyrus are largely unknown. Hippocampal dentate gyrus (HDG) has been shown to express high level of brain-derived neurotrophic factor (BDNF). Here we reported that when BDNF is conditionally knockout in the postnatal-born granular neurons of the HDG, the mutant neurons exhibit aberrant morphological development with less dendritic branches, shorter dendritic length, and lower density of dendritic spines, while their primary dendrites are not obviously affected. Even though, these BDNF-deficient granular neurons develop immature dendritic spines to initiate synaptic contacts with afferent axons, they fail to develop or maintain mature spine structures. Thus, these postnatal-born neurons have fewer numbers of synapses, particularly mature synaptic spines. These results suggest that BDNF plays an important role during dendritic development, synaptic formation and synaptic maturation in postnatal-born granular neurons of the HDG in vivo.