The organization of serotonergic fibers in the Pacific angelshark brain: Neuroanatomical and supercomputing analyses

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 (Squatina
californica), 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.