Coizet Veronique, Heilbronner Sarah R, Carcenac Carole, Mailly Philippe, Lehman Julia F, Savasta Marc, David Oivier, Deniau Jean-Michel, Groenewegen Henk J, Haber Suzanne N
INSERM, U1216, F-38000 Grenoble, France.
University of Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000 Grenoble, France.
J Neurosci. 2017 Mar 8;37(10):2539-2554. doi: 10.1523/JNEUROSCI.3304-16.2017. Epub 2017 Feb 3.
Dysfunction of the orbitofrontal (OFC) and anterior cingulate (ACC) cortices has been linked with several psychiatric disorders, including obsessive-compulsive disorder, major depressive disorder, posttraumatic stress disorder, and addiction. These conditions are also associated with abnormalities in the anterior limb of the internal capsule, the white matter (WM) bundle carrying ascending and descending fibers from the OFC and ACC. Furthermore, deep-brain stimulation (DBS) for psychiatric disorders targets these fibers. Experiments in rats provide essential information on the mechanisms of normal and abnormal brain anatomy, including WM composition and perturbations. However, whereas descending prefrontal cortex (PFC) fibers in primates form a well defined and topographic anterior limb of the internal capsule, the specific locations and organization of these fibers in rats is unknown. We address this gap by analyzing descending fibers from injections of an anterograde tracer in the rat ACC and OFC. Our results show that the descending PFC fibers in the rat form WM fascicles embedded within the striatum. These bundles are arranged topographically and contain projections, not only to the striatum, but also to the thalamus and brainstem. They can therefore be viewed as the rat homolog of the primate anterior limb of the internal capsule. Furthermore, mapping these projections allows us to identify the fibers likely to be affected by experimental manipulations of the striatum and the anterior limb of the internal capsule. These results are therefore essential for translating abnormalities of human WM and effects of DBS to rodent models. Psychiatric diseases are linked to abnormalities in specific white matter (WM) pathways, and the efficacy of deep-brain stimulation relies upon activation of WM. Experiments in rodents are necessary for studying the mechanisms of brain function. However, the translation of results between primates and rodents is hindered by the fact that the organization of descending WM in rodents is poorly understood. This is especially relevant for the prefrontal cortex, abnormal connectivity of which is central to psychiatric disorders. We address this gap by studying the organization of descending rodent prefrontal pathways. These fibers course through a subcortical structure, the striatum, and share important organization principles with primate WM. These results allow us to model primate WM effectively in the rodent.
眶额皮质（OFC）和前扣带回皮质（ACC）功能障碍与多种精神疾病有关，包括强迫症、重度抑郁症、创伤后应激障碍和成瘾。这些病症还与内囊前肢的异常有关，内囊前肢是一条白质（WM）束，携带来自眶额皮质和前扣带回皮质的上下行纤维。此外，用于治疗精神疾病的深部脑刺激（DBS）靶向这些纤维。大鼠实验为正常和异常脑解剖结构的机制提供了重要信息，包括白质组成和扰动。然而，灵长类动物中下行的前额叶皮质（PFC）纤维形成了明确且具有拓扑结构的内囊前肢，而这些纤维在大鼠中的具体位置和组织尚不清楚。我们通过分析在大鼠前扣带回皮质和眶额皮质注射顺行示踪剂后的下行纤维来填补这一空白。我们的结果表明，大鼠中的下行前额叶皮质纤维形成嵌入纹状体内的白质束。这些束按拓扑结构排列，不仅包含投射到纹状体的纤维，还包含投射到丘脑和脑干的纤维。因此，它们可被视为灵长类动物内囊前肢在大鼠中的同源物。此外，绘制这些投射图谱使我们能够识别可能受到纹状体和内囊前肢实验操作影响的纤维。因此，这些结果对于将人类白质异常和深部脑刺激的效果转化为啮齿动物模型至关重要。精神疾病与特定白质（WM）通路的异常有关，深部脑刺激的疗效依赖于白质的激活。啮齿动物实验对于研究脑功能机制是必要的。然而，灵长类动物和啮齿动物之间结果的转化受到以下事实的阻碍：啮齿动物中下行白质的组织情况了解甚少。这对于前额叶皮质尤为重要，其异常连接是精神疾病的核心。我们通过研究啮齿动物下行前额叶通路的组织来填补这一空白。这些纤维穿过一个皮质下结构——纹状体，并与灵长类动物白质共享重要的组织原则。这些结果使我们能够在啮齿动物中有效地模拟灵长类动物白质。
