Aix Marseille Université, Inserm, INMED, Turing Center for Living Systems, Marseille, France.
Elife. 2021 Nov 1;10:e69270. doi: 10.7554/eLife.69270.
Cellular diversity supports the computational capacity and flexibility of cortical circuits. Accordingly, principal neurons at the CA1 output node of the murine hippocampus are increasingly recognized as a heterogeneous population. Their genes, molecular content, intrinsic morpho-physiology, connectivity, and function seem to segregate along the main anatomical axes of the hippocampus. Since these axes reflect the temporal order of principal cell neurogenesis, we directly examined the relationship between birthdate and CA1 pyramidal neuron diversity, focusing on the ventral hippocampus. We used a genetic fate-mapping approach that allowed tagging three groups of age-matched principal neurons: pioneer, early-, and late-born. Using a combination of neuroanatomy, slice physiology, connectivity tracing, and cFos staining in mice, we show that birthdate is a strong predictor of CA1 principal cell diversity. We unravel a subpopulation of pioneer neurons recruited in familiar environments with remarkable positioning, morpho-physiological features, and connectivity. Therefore, despite the expected plasticity of hippocampal circuits, given their role in learning and memory, the diversity of their main components is also partly determined at the earliest steps of development.
细胞多样性支持皮质回路的计算能力和灵活性。相应地，在鼠海马体 CA1 输出节点的主要神经元越来越被认为是一个异质群体。它们的基因、分子含量、内在形态生理学、连接和功能似乎沿着海马体的主要解剖轴分离。由于这些轴反映了主要细胞神经发生的时间顺序，我们直接研究了出生时间与 CA1 锥体神经元多样性之间的关系，重点关注腹侧海马体。我们使用了一种遗传命运映射方法，该方法允许标记三组年龄匹配的主要神经元：先驱、早期和晚期出生的神经元。通过在小鼠中结合神经解剖学、切片生理学、连接追踪和 cFos 染色，我们表明出生时间是 CA1 主要神经元多样性的一个强有力的预测因子。我们揭示了在熟悉环境中招募的先驱神经元的亚群，具有显著的定位、形态生理学特征和连接性。因此，尽管海马回路具有预期的可塑性，但鉴于它们在学习和记忆中的作用，其主要成分的多样性在发育的最早阶段也部分确定。
