Structure-function integrity of the adult hippocampus depends on the transcription factor Bcl11b/Ctip2

Abstract

© 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society. The dentate gyrus is one of the only two brain regions where adult neurogenesis occurs. Throughout life, cells of the neuronal stem cell niche undergo proliferation, differentiation and integration into the hippocampal neural circuitry. Ongoing adult neurogenesis is a prerequisite for the maintenance of adult hippocampal functionality. Bcl11b, a zinc finger transcription factor, is expressed by postmitotic granule cells in the developing as well as adult dentate gyrus. We previously showed a critical role of Bcl11b for hippocampal development. Whether Bcl11b is also required for adult hippocampal functions has not been investigated. Using a tetracycline-dependent inducible mouse model under the control of the forebrain-specific CaMKIIα promoter, we show here that the adult expression of Bcl11b is essential for survival, differentiation and functional integration of adult-born granule cell neurons. In addition, Bcl11b is required for survival of pre-existing mature neurons. Consequently, loss of Bcl11b expression selectively in the adult hippocampus results in impaired spatial working memory. Together, our data uncover for the first time a specific role of Bcl11b in adult hippocampal neurogenesis and function.