Phosphatidic acid (PA) is a signaling lipid involved in the modulation of synaptic structure and functioning. Based on previous work showing a decreasing PA gradient along the longitudinal axis of the rodent hippocampus, we asked whether the dorsal hippocampus (DH) and the ventral hippocampus (VH) are differentially affected by PA modulation. Here, we show that phospholipase D1 (PLD1) is a major hippocampal PA source, compared to PLD2, and that PLD1 ablation affects predominantly the lipidome of the DH. Moreover, Pld1 knockout (KO) mice show specific deficits in novel object recognition and social interaction and disruption in the DH-VH dendritic arborization differentiation in CA1/CA3 pyramidal neurons. Also, Pld1 KO animals present reduced long-term depression (LTD) induction and reduced GluN2A and SNAP-25 protein levels in the DH. Overall, we observe that PLD1-derived PA reduction leads to differential lipid signatures along the longitudinal hippocampal axis, predominantly affecting DH organization and functioning.

磷脂酸（PA）是一种信号脂质，参与突触结构和功能的调节。根据先前的研究显示，沿啮齿类动物海马的纵轴PA梯度降低，我们询问PA调制是否对背侧海马（DH）和腹侧海马（VH）产生了不同的影响。在这里，我们显示磷脂酶D1（PLD1）是海马PA的主要来源，与PLD2相比，PLD1的消融主要影响DH的脂质组。此外，Pld1基因敲除（KO）小鼠在CA1 / CA3锥体神经元的DH-VH树突状乔化分化中显示出新颖的对象识别和社交互动以及破坏中的特定缺陷。另外，Pld1KO动物表现出减少的长期抑郁症（LTD）诱导和DH中的GluN2A和SNAP-25蛋白水平降低。总体而言，我们观察到，PLD1衍生的PA减少导致沿海马纵轴的脂质差异明显，主要影响DH的组织和功能。