Abstract

The autonomic brainstem generates and modifies breathing rhythm by integrating inputs from chemo- and mechanosensors in the viscera while coordinating descending outputs from higher CNS structures. Hypoglossal motoneurons (XII MNs) receive inputs from respiratory premotor neurons in the medulla. Previous studies in rodents have demonstrated significant changes in breathing control during the first three weeks of life, with a sensitive period at 10 to 13 days post-birth (P10–P13) characterized by pronounced changes in neurotransmitters, receptors, excitation-inhibition balance, and breathing. However, age-dependent morphological changes of XII MNs during the first three weeks post-birth and especially during this sensitive period, have not been thoroughly studied. In this study, we comprehensively characterized and quantified the postnatal morphological changes in rat XII MNs. We hypothesized that morphological changes occur in XII MN morphology and arbor complexity corresponding to the functionally-defined sensitive period observed at P10–P13. To test this hypothesis, we used innovative statistical approaches to quantify and compare developmental changes in Golgi-Cox stained XII MNs at nine postnatal ages between P1–P21. Additionally, we performed 3D reconstructions of the neurons importing these geometries into the modeling environment NEURON to simulate the biophysical properties of XII MNs. Soma size increased ~40% from P1 to P21, with no significant change in shape. However, dendritic arborization increased in extent and complexity with branching of neurons significantly increasing from P1 through P13, with the greatest increase at P10–P13 based on the Sholl method. Three age groups 1) P1–P5, 2) P7–P12, and 3) P13–P21 were found as possible windows of development. We also found that at specific ages certain parameters such as soma size and dendritic complexity were non-normally distributed. I found support for differences in the density of selected voltage-gated ion channels with age and correlations between passive electrophysiological properties and morphology. Although a direct relationship was not found between morphology and the active properties, I did find support for an indirect relationship. Our detailed characterization of XII MN morphological development establishes a foundation for the study and elucidation of morphological changes caused by maternal and perinatal conditions using a rigorous approach.

LLU Discipline

Physiology

Department

Basic Sciences

School

School of Medicine

First Advisor

Wilson, Christopher G.

Second Advisor

Bellinger, Denise L.

Third Advisor

Buchholz, John N.

Fourth Advisor

Oberg, Kerby C.

Fifth Advisor

Wilson, Sean M.

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2018

Date (Title Page)

6-2018

Language

English

Library of Congress/MESH Subject Headings

Cranial Nerves; Brain Stem; Rats; Motor Neurons

Subject - Local

Autonomic Brainstem; Breathing Rhythm; Morphology

Type

Dissertation

Page Count

146

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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