The maintenance of specific aspects of neuronal function and behavior is dependent on programmed cell death of adult-generated neurons in the dentate gyrus

A considerable number of new neurons are generated daily in the dentate gyrus (DG) of the adult hippocampus, but only a subset of these survive, as many adult-generated neurons undergo programmed cell death (PCD). However, the significance of PCD in the adult brain for the functionality of DG circuits is not known. Here, we examined the electrophysiological and behavioral characteristics of Bax-knockout ( Bax-KO) mice in which PCD of post-mitotic neurons is prevented. The continuous increase in DG cell numbers in Bax-KO mice resulted in the readjustment of afferent and efferent synaptic connections, represented by age-dependent reductions in the dendritic arborization of DG neurons and in the synaptic contact ratio of mossy fibers with CA3 dendritic spines. These neuroanatomical changes were associated with reductions in synaptic transmission and reduced performance in a contextual fear memory task in 6-month-old Bax-KO mice. These results suggest that the elimination of excess DG neurons via Bax-dependent PCD in the adult brain is required for the normal organization and function of the hippocampus.This work was supported by the Korean Ministry of Science and Technology (grant M10412000078-04N1200-07810 to W. Sun), the 21C Frontier Brain Research Center (grant M103KV010018-03K2201-01820 to H. Kim), KOSEF (grant R01-2004-000-10613-0 to S. Choi) and the NIH (grants NS20402 and NS048982 to R. W. Oppenheim)