Empirical and theoretical work suggests that early postnatal experience may inform later developing synaptic connectivity to adapt the brain to its environment. We hypothesized that early maternal experience may program the development of synaptic density on long range frontal cortex projections. To test this idea, we used maternal separation (MS) to generate environmental variability and examined how MS affected 1) maternal care and 2) synapse density on virally-labeled long range axons of offspring reared in MS or control conditions. We found that MS and variation in maternal care predicted bouton density on dorsal frontal cortex axons that terminated in the basolateral amygdala (BLA) and dorsomedial striatum (DMS) with more, fragmented care associated with higher density. The effects of maternal care on these distinct axonal projections of the frontal cortex were manifest at different ages. Maternal care measures were correlated with frontal cortex → BLA bouton density at mid-adolescence postnatal (P) day 35 and frontal cortex → DMS bouton density in adulthood (P85). Meanwhile, we found no evidence that MS or maternal care affected bouton density on ascending orbitofrontal cortex (OFC) or BLA axons that terminated in the dorsal frontal cortices. Our data show that variation in early experience can alter development in a circuit-specific and age-dependent manner that may be relevant to understanding the effects of early life adversity.

实证和理论工作表明，早期的产后经历可能会为后来发展突触连接提供信息，以使大脑适应其环境。我们假设早期的母体经历可能会影响远距离额叶皮层投射的突触密度的发展。为了测试这个想法，我们使用母体分离 (MS) 来产生环境可变性，并检查 MS 如何影响 1) 母体护理和 2) 在 MS 或对照条件下饲养的后代的病毒标记的远程轴突上的突触密度。我们发现 MS 和母体护理的变化预测了背侧额叶皮层轴突的 bouton 密度，该轴突终止于基底外侧杏仁核 (BLA) 和背内侧纹状体 (DMS)，更多、零散的护理与更高的密度相关。母体照料对额叶皮层这些不同的轴突投射的影响在不同年龄表现出来。产妇护理措施与青春期中期 (P) 第 35 天的额叶皮层 → BLA 布顿密度和成年期额叶皮层 → DMS 布顿密度 (P85) 相关。同时，我们没有发现 MS 或母体护理影响上升眶额皮层 (OFC) 或终止于背额叶皮层的 BLA 轴突的布顿密度的证据。我们的数据表明，早期经历的变化可以以特定电路和年龄相关的方式改变发育，这可能与了解早期生活逆境的影响有关。产妇护理措施与青春期中期 (P) 第 35 天的额叶皮层 → BLA 布顿密度和成年期的额叶皮层 → DMS 布顿密度 (P85) 相关。同时，我们没有发现 MS 或母体护理影响上升眶额皮层 (OFC) 或终止于背额叶皮层的 BLA 轴突的布顿密度的证据。我们的数据表明，早期经历的变化可以以特定电路和年龄相关的方式改变发育，这可能与了解早期生活逆境的影响有关。产妇护理措施与青春期中期 (P) 第 35 天的额叶皮层 → BLA 布顿密度和成年期额叶皮层 → DMS 布顿密度 (P85) 相关。同时，我们没有发现 MS 或母体护理影响上升眶额皮层 (OFC) 或终止于背额叶皮层的 BLA 轴突的布顿密度的证据。我们的数据表明，早期经历的变化可以以特定电路和年龄相关的方式改变发育，这可能与了解早期生活逆境的影响有关。