TY - JOUR T1 - Functional integration of adult-born hippocampal neurons after traumatic brain injury JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0056-15.2015 SP - ENEURO.0056-15.2015 AU - Villasana L. E. AU - Kim K. N. AU - Westbrook G. L. AU - Schnell E. Y1 - 2015/09/15 UR - http://www.eneuro.org/content/early/2015/09/15/ENEURO.0056-15.2015.abstract N2 - Traumatic brain injury (TBI) increases hippocampal neurogenesis, which may contribute to cognitive recovery after injury. However, it is unknown whether TBI-induced adult-born neurons mature normally and functionally integrate into the hippocampal network. We assessed the generation, morphology and synaptic integration of new hippocampal neurons after a controlled cortical impact (CCI) injury model of TBI. To label TBI-induced newborn neurons, we used 2-month-old POMC-eGFP mice, which transiently and specifically express eGFP in immature hippocampal neurons, and Doublecortin-CreERT2 transgenic mice crossed with Rosa26-CAG-tdTomato reporter mice, to permanently pulse-label a cohort of adult-born hippocampal neurons. TBI increased the generation, outward migration, and dendritic complexity of neurons born during post-traumatic neurogenesis. Cells born after TBI had profound alterations in their dendritic structure, with increased dendritic branching proximal to the soma and widely splayed dendritic branches. These changes were apparent during early dendritic outgrowth, and persisted as these cells matured. Whole-cell recordings from neurons generated during post-traumatic neurogenesis demonstrate that they are excitable and functionally integrate into the hippocampal circuit. However, despite their dramatic morphologic abnormalities, we found no differences in the rate of their electrophysiologic maturation, or their overall degree of synaptic integration when compared to age-matched adult-born cells from sham mice. Our results suggest that cells born after TBI participate in information processing, and receive an apparently normal balance of excitatory and inhibitory inputs. However, TBI-induced changes in their anatomic localization and dendritic projection patterns could result in maladaptive network properties.Significance Statement: Post-traumatic neurogenesis may contribute to recovery after TBI, but the functional integrity of neurons generated after injury is critical and has not yet been examined. We used multiple lines of transgenic mice to label cells born after TBI in order to study their maturation and synaptic integration. Although cells born after TBI had significantly altered morphology and anatomic localization, they functionally integrated into the hippocampal circuit. Our data indicate that these adult-born neurons contribute to network connectivity after TBI, although changes in their morphology and dendritic projection patterns may alter their functional capacity. ER -