FENS Forum of European Neuroscience edition:7 location:Amsterdam date:3 - 7 July 2010
In adult mammals, newborn neural precursor cells (NPCs) derived from either the subventricular zone (SVZ) or the subgranular zone (SGZ) migrate into the olfactory bulb and the dentate gyrus, respectively, where some of them mature into excitatory and inhibitory neurons. There is increasing evidence that this process is important for some types of learning and synaptic plasticity and vice versa. Survivin, a member of the inhibitor of apoptotis protein (IAP) family, is abundantly expressed in nervous tissue during embryonic development while being restricted postnatally to proliferating and migrating NPCs in SVZ and SGZ. Here we examined adult SurvivinCamcre mice with a prenatal conditional deletion of the survivin gene in SVZ and SGZ that results in a diminished neurogenesis as indicated by reduced numbers of SVZ NPCs and an absent rostral migratory stream.
We investigated long-term potentiation (LTP) in dentate gyrus (DG) and CA1-region as well as hippocampus-dependent types of learning. Although deletion of survivin had no effect on basic excitability in DG and CA1-region, there was a marked impairment of LTP in these areas. When SurvivinCamcre mice were tested in hippocampus-dependent types of learning, we found significant deficits in Morris water maze, context-dependent fear conditioning and passive avoidance learning. Our data support a key function of survivin in hippocampal synaptic plasticity and learning and underline the outstanding importance of adult brain neurogenesis for proper operation of the hippocampal tri-synaptic circuit and the physiological functions that depend on it.