Distribution & Density of 5-HT Fibers in the Lumbar Spinal Cord of the Mouse Public

Patel, Nikita (Spring 2023)

Permanent URL: https://etd.library.emory.edu/concern/etds/ww72bc957?locale=fr
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Abstract

Serotonergic (5-HT) neurons in the raphe nuclei of the brainstem profusely innervate every part of the central nervous system (CNS) to exert a breadth of modulatory functions, including regulating spinal motor circuits. The existing literature has reported complex and sometimes conflicting actions of 5-HT on spinal motor circuits. This has been attributed to methodological differences (species, age, etc.) and a lack of approaches that would enable the specific activation of the 5-HT raphe neurons projecting to the spinal cord (5-HT raphe-spinal neurons) without activation of the non-5-HT raphe-spinal neurons. Now that such a specific approach is possible in the mouse (Giorgi & Perreault, 2021), it is critical that we gather information about the anatomy of the 5-HT raphe-spinal system in this species. Therefore, this study aims to assess the laminar and funicular distribution and density of 5-HT raphe-spinal fibers projecting to the upper lumbar segments of the spinal cord, where core circuits of hindlimb movements are found, both in newborn mice and in young adult mice. We find approximately 53% more 5-HT axon segments in the ventral horn of the neonate compared to the adult mouse. In addition, we report the ventral and lateral funiculi of the neonate mouse having over three times the number of 5-HT axon segments than the adult mouse. One hypothesis for this large drop in fibers with age is proposed by ten Donkelaar, who suggests redundant axons are selectively reduced following collateralization in the spinal cord.

Table of Contents

1) Purpose

2) Background

2) Serotonergic (5-HT) Neurons

4) 5-HT Fiber Development in the Mouse

4) 5-HT Fiber Morphology

5) Methods

5) Perfusion & Tissue Preparation

5) Sectioning

6) Immunohistochemistry

7) Imaging & Analysis

9) Troubleshooting

11) Results

11) 5-HT Fibers in the Gray Matter

14) 5-HT Fibers in the White Matter

15) Other Statistical Analyses

16) Discussion

16) Decrease in 5-HT Fibers in the Ventral Gray Matter

17) Decrease in 5-HT Fibers across the White Matter Funiculi

18) Strengths of Study

18) Limitations of Study

19) Future Directions

21) References

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