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-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 (MF) 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.
成年海马的齿状回(DG)每天都会产生大量新的神经元,但只有一部分能够存活,因为许多成年后产生的神经元会经历程序性细胞死亡(PCD)。然而,成年大脑中PCD对DG回路功能的重要性尚不清楚。在此,我们研究了Bax基因敲除(Bax - KO)小鼠的电生理和行为特征,这类小鼠有丝分裂后神经元的PCD受到抑制。Bax - KO小鼠DG细胞数量的持续增加导致传入和传出突触连接的重新调整,表现为DG神经元树突分支以及苔藓纤维(MF)与CA3树突棘的突触接触率随年龄增长而降低。这些神经解剖学变化与6个月大的Bax - KO小鼠的突触传递减少以及在情境恐惧记忆任务中的表现下降有关。这些结果表明,成年大脑中通过依赖Bax的PCD消除多余的DG神经元对于海马的正常组织和功能是必需的。