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Mays, K. C.

Publications and source records attributed to Mays, K. C..

2 recordsLinked to original sources

Qualitative Observations of Transgenically Individualized Serotonergic Fibers in the Mouse Telencephalon

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.

neuroscience↗

An Experimental Platform for Stochastic Analyses of Single Serotonergic Fibers in the Mouse Brain

The self-organization of the serotonergic matrix, a massive axon meshwork in all vertebrate brains, is driven by the structural and dynamical properties of its constitutive elements. Each of these elements, a single serotonergic axon (fiber), has a unique trajectory and can be supported by a soma that executes one of many available transcriptional programs. It necessitates the development of specialized methods for single-fiber analyses, both at the experimental and theoretical levels. We developed an integrated system that facilitates experimental isolation of single serotonergic fibers in brain tissue, including regions with high fiber densities, and demonstrated the potential of their quantitative analyses based on stochastic modeling. Single fibers were visualized using two transgenic mouse models, one of which is the first implementation of the Brainbow toolbox in this system. The trajectories of serotonergic fibers were automatically traced in the three spatial dimensions with a novel algorithm, and their properties were captured with a single parameter associated with the directional von Mises-Fisher probability distribution. The system represents an end-to-end workflow that can be imported into various studies, including those investigating serotonergic dysfunction in brain disorders. It also supports new research directions inspired by single-fiber analyses in the serotonergic matrix, including supercomputing simulations and modeling in physics.

neuroscience↗