Qualitative Observations of Transgenically Individualized Serotonergic Fibers in the Mouse Telencephalon

Abstract

The matrix of serotonergic axons (fibers) is a constant feature of neural tissue in vertebrate brains. Its fundamental role appears to be associated with the spatiotemporal control of neuroplasticity. The densities of serotonergic fibers vary across brain regions, but their development and maintenance remain poorly understood. A specific fiber concentration is achieved as the result of the dynamics of a large number of individual fibers, each of which can make trajectory decisions independently of other fibers. Bridging these processes, operating on very different spatial scales, remains a challenge in neuroscience. The study provides the first qualitative description of individually-tagged serotonergic axons in four selected telencephalic regions (cortical and subcortical) of the mouse brain. Based on our previous implementation of the Brainbow toolbox in this system, serotonergic fibers were labeled with random intensity combinations of three fluorophores and imaged with high-resolution confocal microscopy. All examined regions contained serotonergic fibers of diverse identities and morphologies, often traveling in close proximity to one another. Some fibers transitioned among several morphologies in the same imaged volume. High fiber densities appeared to be associated with highly tortuous fiber segments produced by some individual fibers. This study supports efforts to predictively model the self-organization of the serotonergic matrix in all vertebrates, including regenerative processes in the adult human brain.