TY - JOUR T1 - ADAP1/Centaurin-α1 negatively regulates dendritic spine function and memory formation in the hippocampus JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0111-20.2020 SP - ENEURO.0111-20.2020 AU - Erzsebet Szatmari AU - Corey Moran AU - Sarah Cohen AU - Amanda Jacob AU - Paula Parra-Bueno AU - Naomi Kamasawa AU - Debbie Guerrero-Given AU - Michael Klein AU - Robert Stackman, Jr AU - Ryohei Yasuda Y1 - 2020/11/02 UR - http://www.eneuro.org/content/early/2020/10/30/ENEURO.0111-20.2020.abstract N2 - ADAP1/Centaurin-α1 (CentA1) functions as an Arf6 GTPase-activating protein highly enriched in the brain. Previous studies demonstrated the involvement of CentA1 in brain function as a regulator of dendritic differentiation and a potential mediator of Alzheimer’s disease pathogenesis. To better understand the neurobiological functions of CentA1 signaling in the brain, we developed Centa1 knockout mice. The knockout animals showed neither brain development nor synaptic ultrastructure deficits in the hippocampus. However, they exhibited significantly higher density and enhanced structural plasticity of dendritic spines in the CA1 region of the hippocampus compared to non-transgenic littermates. Moreover, the deletion of Centa1 improved performance in the object-in-place spatial memory task. These results suggest that CentA1 functions as a negative regulator of spine density and plasticity, and of hippocampus-dependent memory formation. Thus, CentA1 and its downstream signaling may serve as a potential therapeutic target to prevent memory decline associated with aging and brain disorders.SIGNIFICANCE STATEMENT ADAP1/Centaurin-α1 (CentA1) is highly enriched in the brain and has been shown to be involved in the developmental regulation of dendritic differentiation. Although increased CentA1 level has been linked to Alzheimer’s disease, the underlying neurological mechanisms are unknown. We found that the genetic deletion of Centa1 leads to increased dendritic spine plasticity and enhanced spine structural plasticity in the hippocampus, accompanied by behavioral improvements in a location recognition task. This is the first study of CentA1 role in the brain, and our findings will facilitate the understanding of neurobiological mechanisms underlying the regulation of dendritic spine morphology and plasticity in healthy brains and in neurological disorders. ER -