Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
PLoS One. 2012;7(8):e44236. doi: 10.1371/journal.pone.0044236. Epub 2012 Aug 31.
The lateral septum has strong efferent projections to hypothalamic and midbrain regions, and has been associated with modulation of social behavior, anxiety, fear conditioning, memory-related behaviors, and the mesolimbic reward pathways. Understanding natural variation of lateral septal anatomy and function, as well as its genetic modulation, may provide important insights into individual differences in these evolutionarily important functions. Here we address these issues by using efficient and unbiased stereological probes to estimate the volume of the lateral septum in the BXD line of recombinant inbred mice. Lateral septum volume is a highly variable trait, with a 2.5-fold difference among animals. We find that this trait covaries with a number of behavioral and physiological phenotypes, many of which have already been associated with behaviors modulated by the lateral septum, such as spatial learning, anxiety, and reward-seeking. Heritability of lateral septal volume is moderate (h(2) = 0.52), and much of the heritable variation is caused by a locus on the distal portion of chromosome (Chr) 1. Composite interval analysis identified a secondary interval on Chr 2 that works additively with the Chr 1 locus to increase lateral septum volume. Using bioinformatic resources, we identified plausible candidate genes in both intervals that may influence the volume of this key nucleus, as well as associated behaviors.
外侧隔核有强烈的向下丘脑和中脑区域的传出投射，与调节社会行为、焦虑、恐惧条件反射、与记忆相关的行为以及中脑边缘奖赏通路有关。了解外侧隔核解剖结构和功能的自然变异，以及其遗传调节，可能为这些在进化上重要的功能的个体差异提供重要的见解。在这里，我们使用高效和无偏的立体学探针来估计 BXD 重组近交系小鼠的外侧隔核体积，从而解决这些问题。外侧隔核体积是一个高度可变的特征，动物之间的差异有 2.5 倍。我们发现，这个特征与许多行为和生理表型相关，其中许多表型已经与外侧隔核调节的行为有关，例如空间学习、焦虑和寻求奖励。外侧隔核体积的遗传力适中（h(2) = 0.52），并且大部分可遗传的变异是由染色体（Chr）1的远端部分上的一个基因座引起的。复合区间分析确定了 Chr 2 上的一个次要区间，该区间与 Chr 1 基因座相加，增加了外侧隔核体积。利用生物信息学资源，我们在两个区间中确定了可能影响这个关键核体积以及相关行为的有希望的候选基因。
