Janušonis Skirmantas, Metzler Ralf, Vojta Thomas
Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, United States.
Institute of Physics and Astronomy, University of Potsdam, Potsdam, Germany.
Front Neurosci. 2025 Aug 8;19:1602116. doi: 10.3389/fnins.2025.1602116. eCollection 2025.
Serotonergic axons (fibers) are a universal feature of all vertebrate brains. They form meshworks, typically quantified with regional density measurements, and appear to support neuroplasticity. The self-organization of this system remains poorly understood, partly because of the strong stochasticity of individual fiber trajectories. In an extension to our previous analyses of the mouse brain, serotonergic fibers were investigated in the brain of the Pacific angelshark (), a representative of a unique (ray-like) lineage of the squalomorph sharks. First, the fundamental cytoarchitecture of the angelshark brain was examined, including the expression of ionized calcium-binding adapter molecule 1 (Iba1, AIF-1) and the mesencephalic trigeminal nucleus. Second, serotonergic fibers were visualized with immunohistochemistry, which showed that fibers in the forebrain have the tendency to move toward the dorsal pallium and also accumulate at higher densities at pial borders. Third, a population of serotonergic fibers was modeled inside a digital model of the angelshark brain by using a supercomputing simulation. The simulated fibers were defined as sample paths of reflected fractional Brownian motion (FBM), a continuous-time stochastic process. The regional densities generated by these simulated fibers reproduced key features of the biological serotonergic fiber densities in the telencephalon, a brain division with a considerable physical uniformity and no major "obstacles" (dense axon tracts). These results demonstrate that the paths of serotonergic fibers may be inherently stochastic, and that a large population of such paths can give rise to a consistent, non-uniform, and biologically-realistic fiber density distribution. Local densities may be induced by the constraints of the three-dimensional geometry of the brain, with no axon guidance cues. However, they can be further refined by anisotropies that constrain fiber movement (e.g., major axon tracts, active self-avoidance, chemical gradients). In the angelshark forebrain, such constraints may be reduced to an attractive effect of the dorsal pallium, suggesting that anatomically complex distributions of fiber densities can emerge from the interplay of a small set of stochastic and deterministic processes.
血清素能轴突（纤维）是所有脊椎动物大脑的普遍特征。它们形成网络，通常通过区域密度测量进行量化，并且似乎支持神经可塑性。该系统的自组织仍知之甚少，部分原因是单个纤维轨迹具有很强的随机性。在对我们之前对小鼠大脑分析的扩展研究中，我们对太平洋扁鲨大脑中的血清素能纤维进行了研究，太平洋扁鲨是角鲨目鲨鱼独特（类似鳐鱼）谱系的代表。首先，研究了扁鲨大脑的基本细胞结构，包括离子钙结合衔接分子1（Iba1，AIF - 1）的表达和中脑三叉神经核。其次，通过免疫组织化学观察血清素能纤维，结果表明前脑的纤维倾向于向背侧皮层移动，并且在软脑膜边界处也以更高的密度聚集。第三，利用超级计算机模拟在扁鲨大脑的数字模型中对一群血清素能纤维进行建模。模拟纤维被定义为反射分数布朗运动（FBM）的样本路径，这是一种连续时间随机过程。这些模拟纤维产生的区域密度再现了端脑中生物血清素能纤维密度的关键特征，端脑是一个物理结构相当均匀且没有主要“障碍”（密集轴突束）的脑区。这些结果表明，血清素能纤维的路径可能本质上是随机的，并且大量这样的路径可以产生一致、非均匀且符合生物学现实的纤维密度分布。局部密度可能由大脑三维几何结构的限制诱导产生，而无需轴突导向线索。然而，它们可以通过限制纤维运动的各向异性（例如主要轴突束、主动自我回避、化学梯度）进一步细化。在扁鲨前脑中，这种限制可能简化为背侧皮层的吸引作用，这表明纤维密度的解剖学复杂分布可以从小范围的随机和确定性过程的相互作用中产生。
