Gursky Zachary H, Klintsova Anna Y
Department of Psychological & Brain Sciences, University of Delaware, Newark, DE 19716, USA.
Brain Sci. 2021 Mar 4;11(3):323. doi: 10.3390/brainsci11030323.
Alcohol exposure (AE) during the third trimester of pregnancy-a period known as the brain growth spurt (BGS)-could result in a diagnosis of a fetal alcohol spectrum disorder (FASD), a hallmark of which is impaired executive functioning (EF). Coordinated activity between prefrontal cortex and hippocampus is necessary for EF and thalamic nucleus reuniens (Re), which is required for prefrontal-hippocampal coordination, is damaged following high-dose AE during the BGS. The current experiment utilized high-dose AE (5.25 g/kg/day) during the BGS (i.e., postnatal days 4-9) of Long-Evans rat pups. AE reduces the number of neurons in Re into adulthood and selectively alters the proportion of Re neurons that simultaneously innervate both medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC). The AE-induced change unique to Re→(mPFC + vHPC) projection neurons (neuron populations that innervate either mPFC or vHPC individually were unchanged) is not mediated by reduction in neuron number. These data are the first to examine mPFC-Re-HPC circuit connectivity in a rodent model of FASD, and suggest that both short-term AE-induced neuron loss and long-term changes in thalamic connectivity may be two distinct (but synergistic) mechanisms by which developmental AE can alter mPFC-Re-vHPC circuitry and impair EF throughout the lifespan.
孕期第三个阶段（即大脑发育加速期）的酒精暴露（AE）可能导致胎儿酒精谱系障碍（FASD）的诊断，其一个标志是执行功能（EF）受损。前额叶皮质和海马体之间的协调活动对于执行功能是必要的，而丘脑 reuniens 核（Re）是前额叶 - 海马体协调所必需的，在大脑发育加速期高剂量酒精暴露后会受到损害。当前实验在 Long-Evans 大鼠幼崽的大脑发育加速期（即出生后第4 - 9天）使用了高剂量酒精暴露（5.25克/千克/天）。酒精暴露会减少成年后 Re 中的神经元数量，并选择性地改变同时支配内侧前额叶皮质（mPFC）和腹侧海马体（vHPC）的 Re 神经元比例。酒精暴露诱导的 Re→（mPFC + vHPC）投射神经元的独特变化（单独支配 mPFC 或 vHPC 的神经元群体未改变）不是由神经元数量减少介导的。这些数据首次在胎儿酒精谱系障碍的啮齿动物模型中研究了 mPFC - Re - HPC 回路的连通性，并表明短期酒精暴露诱导的神经元损失和丘脑连通性的长期变化可能是发育性酒精暴露在整个生命周期中改变 mPFC - Re - vHPC 电路并损害执行功能的两种不同（但协同）机制。
