Fibroblast growth factor receptor 2 (FGFR2) is almost exclusively expressed in glial cells in postnatal mouse brain, but its impact in glia for brain behavioral functioning is poorly understood. We compared behavioral effects from FGFR2 loss in both neurons and astroglial cells and from FGFR2 loss in astroglial cells by using either the pluripotent progenitor-driven hGFAP-cre or the tamoxifen-inducible astrocyte-driven GFAP-creER^T2 in Fgfr2 floxed mice. When FGFR2 was eliminated in embryonic pluripotent precursors or in early postnatal astroglia, mice were hyperactive, and had small changes in working memory, sociability, and anxiety-like behavior. In contrast, FGFR2 loss in astrocytes starting at 8 weeks of age resulted only in reduced anxiety-like behavior. Therefore, early postnatal loss of FGFR2 in astroglia is critical for broad behavioral dysregulation. Neurobiological assessments demonstrated that astrocyte-neuron membrane contact was reduced and glial glutamine synthetase expression increased only by early postnatal FGFR2 loss. We conclude that altered astroglial cell function dependent on FGFR2 in the early postnatal period may result in impaired synaptic development and behavioral regulation, modeling childhood behavioral deficits like attention deficit hyperactivity disorder (ADHD).

成纤维细胞生长因子受体 2 (FGFR2) 几乎只在出生后小鼠大脑的神经胶质细胞中表达，但其在神经胶质细胞中对大脑行为功能的影响却知之甚少。我们通过在Fgfr2 floxed 小鼠中使用多能祖细胞驱动的hGFAP-cre或他莫昔芬诱导的星形胶质细胞驱动的GFAP-creER ^T2 ，比较了神经元和星形胶质细胞中 FGFR2 丢失以及星形胶质细胞中 FGFR2 丢失的行为影响。当胚胎多能前体细胞或出生后早期星形胶质细胞中的 FGFR2 被消除时，小鼠变得过度活跃，并且工作记忆、社交能力和焦虑样行为发生微小变化。相比之下，星形胶质细胞从 8 周龄开始丧失 FGFR2 仅导致焦虑样行为减少。因此，出生后早期星形胶质细胞中 FGFR2 的缺失对于广泛的行为失调至关重要。神经生物学评估表明，星形胶质细胞-神经元膜接触减少，神经胶质谷氨酰胺合成酶表达仅因出生后早期 FGFR2 缺失而增加。我们的结论是，出生后早期依赖于 FGFR2 的星形胶质细胞功能的改变可能会导致突触发育和行为调节受损，从而模拟儿童行为缺陷，例如注意力缺陷多动障碍 (ADHD)。