Adult hippocampal neurogenesis (AHN) is a form of ongoing plasticity in the brain that supports specific aspects of cognition. Disruptions in AHN have been observed in neuropsychiatric conditions presenting with inflammatory components and are associated with impairments in cognition and mood. Recent evidence highlights important roles of the complement system in synaptic plasticity and neurogenesis during neurodevelopment and in acute learning and memory processes. In this work we investigated the impact of the complement C3/C3aR pathway on AHN and its functional implications for AHN-related behaviours. In C3^−/− mice, we found increased numbers and accelerated migration of adult born granule cells, indicating that absence of C3 leads to abnormal survival and distribution of adult born neurons. Loss of either C3 or C3aR affected the morphology of immature neurons, reducing morphological complexity, though these effects were more pronounced in the absence of C3aR. We assessed functional impacts of the cellular phenotypes in an operant spatial discrimination task that assayed AHN sensitive behaviours. Again, we observed differences in the effects of manipulating C3 or C3aR, in that whilst C3aR^−/− mice showed evidence of enhanced pattern separation abilities, C3^−/− mice instead demonstrated impaired behavioural flexibility. Our findings show that C3 and C3aR manipulation have distinct effects on AHN that impact at different stages in the development and maturation of newly born neurons, and that the dissociable cellular phenotypes are associated with specific alterations in AHN-related behaviours.

成人海马神经发生（AHN）是大脑中持续可塑性的一种形式，支持特定的认知方面。在具有炎症成分的神经精神疾病中观察到 AHN 的破坏，并且与认知和情绪损害相关。最近的证据强调了补体系统在神经发育以及急性学习和记忆过程中的突触可塑性和神经发生中的重要作用。在这项工作中，我们研究了补体 C3/C3aR 通路对 AHN 的影响及其对 AHN 相关行为的功能影响。在C3 ^−/−小鼠中，我们发现成年颗粒细胞的数量增加并加速迁移，表明 C3 的缺失会导致成年神经元的异常存活和分布。C3 或 C3aR 的缺失会影响未成熟神经元的形态，降低形态复杂性，尽管这些影响在 C3aR 缺失的情况下更为明显。我们在分析 AHN 敏感行为的操作性空间辨别任务中评估了细胞表型的功能影响。我们再次观察到操纵 C3 或 C3aR 的效果存在差异，因为虽然C3aR ^−/−小鼠显示出模式分离能力增强的证据，但C3 ^−/−小鼠却表现出行为灵活性受损。我们的研究结果表明，C3 和 C3aR 操作对 AHN 具有明显的影响，会影响新生神经元发育和成熟的不同阶段，并且可分离的细胞表型与 AHN 相关行为的特定改变相​​关。